This review article discusses the potential use of mesenchymal stem cells (MSCs) in cancer therapy. MSCs can be obtained from sources like bone marrow and adipose tissue. They have properties like homing to tumor sites and secreting factors that may help reduce tumor growth. However, there are challenges to using MSCs in cancer therapy. Extensive expansion of MSCs in vitro carries a risk of malignant transformation due to telomere shortening or manipulation. There is also a limited understanding of the molecular mechanisms underlying any potential malignant transformation. Overall, while MSCs show promise as delivery vehicles for anti-cancer agents due to their homing properties, more research is needed to fully understand and address the risks of their therapeutic
Cancer stem cells (CSCs) are a small subpopulation of cells within tumors that drive tumor growth and metastasis. They express cell surface markers like CD44 and CD133 and have the ability to self-renew and differentiate. CSCs are resistant to chemotherapy and radiation therapy due to their slow proliferation rate, expression of drug efflux pumps, and increased DNA damage response. Epithelial-mesenchymal transition (EMT) and signaling pathways like TGF-β, WNT and NOTCH regulate CSC properties. Targeting CSCs, their microenvironment, and these pathways may help overcome therapy resistance and prevent cancer recurrence. Identification of CSCs involves flow cytometry analysis of surface markers, dye efflux assays,
This study investigated how acellular gelatinous Wharton's jelly (AGWJ) enhances skin wound healing. Through proteomics analysis, they detected proteins characteristic of exosomes in AGWJ. Exosomes were isolated from AGWJ using ultracentrifugation. In vitro, these exosomes enhanced fibroblast viability and migration. In a mouse model of skin wounds, treatment with AGWJ exosomes enhanced wound healing. Mass spectrometry analysis revealed that AGWJ exosomes contain high amounts of alpha-2-macroglobulin, a protein that likely mimics the wound healing effects of AGWJ exosomes. Therefore, exosomes and their cargo, such as alpha-2-macroglobulin,
This document discusses the potential use of mesenchymal stem cells (MSCs) derived from Wharton's jelly (WJ) of the human umbilical cord for regenerative medicine applications. MSCs from WJ present several advantages over other stem cell sources, including reduced immunogenicity, increased proliferative capacity, and ability to differentiate into various cell types. The document reviews potential applications of WJ-MSCs in cell therapy for cancer, liver disease, peripheral nerve damage, cardiovascular and connective tissue repair, and obesity/diabetes. However, challenges remain in optimizing isolation methods and tracking techniques for clinical applications of WJ-MSCs.
Cancer stem cell theory and evidence from colorecatalKareem Ahmed
This is a presentation of a review article explaining theory of cancer stem cells with evidences from colorectal cancer at a glance. It was presented at Student Research Symposium at Faculty OF Medicine, Assiut University, Assiut, Egypt,
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
Control of Cancer Stem Cell Migration and invasionGirish Kumar K
Cancer stem cells are rare cells within tumors that can self-renew and generate all cell types in a tumor. They are responsible for tumor initiation and driving metastasis. Cancer stem cells are identified through sphere formation assays, flow cytometry to detect drug efflux pumps, and cell surface marker expression. They can be isolated from tumors using fluorescence-activated cell sorting or magnetic-activated cell sorting based on specific cell surface markers. Targeting cancer stem cells may help control metastasis and tumor relapse.
This document summarizes the biology and potential clinical applications of mesenchymal stem cells (MSCs) derived from the Wharton's jelly of the umbilical cord. It discusses how MSCs were originally isolated from bone marrow but umbilical cord is now seen as a promising alternative source due to its abundance of MSCs and the non-invasive collection method. MSCs from Wharton's jelly (WJ-MSCs) share properties with bone marrow MSCs yet are considered more primitive. The review examines the multilineage potential and immunomodulatory abilities of WJ-MSCs and their emerging roles in treating cancer, graft-versus-host disease, and systemic lupus erythemat
Cancer stem cells (CSCs) are a small subpopulation of cells within tumors that drive tumor growth and metastasis. They express cell surface markers like CD44 and CD133 and have the ability to self-renew and differentiate. CSCs are resistant to chemotherapy and radiation therapy due to their slow proliferation rate, expression of drug efflux pumps, and increased DNA damage response. Epithelial-mesenchymal transition (EMT) and signaling pathways like TGF-β, WNT and NOTCH regulate CSC properties. Targeting CSCs, their microenvironment, and these pathways may help overcome therapy resistance and prevent cancer recurrence. Identification of CSCs involves flow cytometry analysis of surface markers, dye efflux assays,
This study investigated how acellular gelatinous Wharton's jelly (AGWJ) enhances skin wound healing. Through proteomics analysis, they detected proteins characteristic of exosomes in AGWJ. Exosomes were isolated from AGWJ using ultracentrifugation. In vitro, these exosomes enhanced fibroblast viability and migration. In a mouse model of skin wounds, treatment with AGWJ exosomes enhanced wound healing. Mass spectrometry analysis revealed that AGWJ exosomes contain high amounts of alpha-2-macroglobulin, a protein that likely mimics the wound healing effects of AGWJ exosomes. Therefore, exosomes and their cargo, such as alpha-2-macroglobulin,
This document discusses the potential use of mesenchymal stem cells (MSCs) derived from Wharton's jelly (WJ) of the human umbilical cord for regenerative medicine applications. MSCs from WJ present several advantages over other stem cell sources, including reduced immunogenicity, increased proliferative capacity, and ability to differentiate into various cell types. The document reviews potential applications of WJ-MSCs in cell therapy for cancer, liver disease, peripheral nerve damage, cardiovascular and connective tissue repair, and obesity/diabetes. However, challenges remain in optimizing isolation methods and tracking techniques for clinical applications of WJ-MSCs.
Cancer stem cell theory and evidence from colorecatalKareem Ahmed
This is a presentation of a review article explaining theory of cancer stem cells with evidences from colorectal cancer at a glance. It was presented at Student Research Symposium at Faculty OF Medicine, Assiut University, Assiut, Egypt,
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
Control of Cancer Stem Cell Migration and invasionGirish Kumar K
Cancer stem cells are rare cells within tumors that can self-renew and generate all cell types in a tumor. They are responsible for tumor initiation and driving metastasis. Cancer stem cells are identified through sphere formation assays, flow cytometry to detect drug efflux pumps, and cell surface marker expression. They can be isolated from tumors using fluorescence-activated cell sorting or magnetic-activated cell sorting based on specific cell surface markers. Targeting cancer stem cells may help control metastasis and tumor relapse.
This document summarizes the biology and potential clinical applications of mesenchymal stem cells (MSCs) derived from the Wharton's jelly of the umbilical cord. It discusses how MSCs were originally isolated from bone marrow but umbilical cord is now seen as a promising alternative source due to its abundance of MSCs and the non-invasive collection method. MSCs from Wharton's jelly (WJ-MSCs) share properties with bone marrow MSCs yet are considered more primitive. The review examines the multilineage potential and immunomodulatory abilities of WJ-MSCs and their emerging roles in treating cancer, graft-versus-host disease, and systemic lupus erythemat
This literature review finds that umbilical cord tissue, specifically Wharton's jelly, offers the greatest number of harvestable mesenchymal stem cells. The review analyzed 161 studies reporting mesenchymal stem cell yields from various tissue sources, including adipose tissue, bone marrow, umbilical cord tissue, and placental tissue. It found that yields from umbilical cord tissue ranged from 10,000 to 4,700,000 cells per milliliter, far exceeding yields from other sources. Adipose tissue provided the next highest yields, ranging from 4,737 to 1,550,000 cells per milliliter. Bone marrow yields ranged more widely from 1 to 317,400 cells per millil
This document discusses cancer stem cells (CSCs), which are cells that can self-renew and differentiate to produce the heterogeneous cells that comprise a tumor. The stem cell theory of cancer proposes that CSCs, like normal stem cells, sustain cancer growth. CSCs share similarities with normal stem cells such as long lifespans and resistance to apoptosis. Researchers are investigating whether CSCs arise from normal stem cells, progenitor cells, or differentiated cells in adult tissue. While CSCs have been identified in hematopoietic and solid tumors, their discovery has opened new avenues for cancer therapies that target these cells specifically.
Cell within a tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor”.
“CSC can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”.
Mammalian MSC from Selected Species: Features and Applications
Christiane Uder, Sandra Br€uckner, Sandra Winkler, Hans-Michael Tautenhahn,†‡ Bruno Christ†*
Mesenchymal stromal/stem cells (MSC) are promising candidates for cellular therapy of different diseases in humans and in animals. Following the guidelines of the International Society for Cell Therapy, human MSC may be identified by expression of a specific panel of cell surface markers (CD1051, CD731, CD901, CD34-, CD14-, or CD11b-, CD79- or CD19-, HLA-DR-). In addition, multiple differentiation potential into at least the osteogenic, adipogenic, and chondrogenic lineage is a main criterion for MSC definition. Human MSC and MSC of a variety of mammals isolated from different tissues meet these criteria. In addition to the abovementioned, they express many more cell surface markers. Yet, these are not uniquely expressed by MSC. The gross phenotypic appearance like marker expression and differentiation potential is similar albeit not identical for MSC from different tissues and species. Similarly, MSC may feature different biological characteristics depending on the tissue source and the isolation and culture procedures. Their versatile biological qualities comprising immunomodulatory, anti-inflammatory, and proregenerative capacities rely largely on the migratory and secretory capabilities of MSC. They are attracted to sites of tissue lesion and secrete factors to promote self-repair of the injured tissue. This is a big perspective for clinical MSC applications in both veterinary and human medicine. Phase I/II clinical trials have been initiated to assess safety and feasibility of MSC therapies in acute and chronic disease settings. Yet, since the mode of MSC action in a specific disease environment is still unknown at large, it is mandatory to unravel the response of MSC from a given source onto a specific disease environment in suitable animal models prior to clinical applications.
Umbilical cord mesenchymal stem cells (UC-MSCs) show potential advantages over mesenchymal stem cells (MSCs) from other sources for regenerative medicine applications. UC-MSCs display higher proliferation rates and expression of embryonic genes compared to adult MSCs. Transcriptomic analyses indicate UC-MSCs express genes related to development of multiple tissues including bone, liver, cardiovascular and neural systems. While UC-MSCs can differentiate into cell types of multiple lineages, their therapeutic impact is thought to be mainly due to their paracrine effects and immunomodulatory properties. UC-MSCs could have advantages for treating autoimmune and neurodegenerative diseases.
Wharton’s jelly mesenchymal stem cells as off the-shelf cellular therapeutics...raditio ghifiardi
This document discusses Wharton's jelly mesenchymal stem cells (WJMSCs) and their potential as an alternative to bone marrow mesenchymal stem cells (BMMSCs) for regenerative therapies. WJMSCs are isolated from the umbilical cord and have advantages over BMMSCs such as easier accessibility, higher proliferation rates, and greater consistency between samples. Studies show that WJMSCs secrete trophic and immunomodulatory factors that aid tissue repair. However, more research is needed to understand how well WJMSCs can engraft and survive in allogeneic transplant settings and their exact immune modulation mechanisms. The document reviews the immune regulatory properties of WJMSCs
Development of cancer therapeutics is often carried out in 2D cultures prior to testing on animal model. In comparison to 2D cultures, discuss the potential of using 3D in vitro models for drug efficiency testing.
3D In Vitro Models for Drug Efficiency TestingTiffany Ho
3D cell cultures more accurately model the in vivo microenvironment compared to traditional 2D cultures. 3D cultures form cell aggregates or spheroids, mimic tumor development, and allow for more effective drug testing compared to flat monolayers. Emerging technologies like organ-on-chip microfluidic devices and 3D printing have the potential to further advance 3D cell culture models by replicating the functions of human organs and embedding living cells in scaffolds.
This chapter discusses perspectives on employing mesenchymal stem cells from Wharton's jelly of the umbilical cord for peripheral nerve repair. It provides background on regenerative medicine and peripheral nerve injuries. Various biomaterials that have been tested as scaffolds for delivering mesenchymal stem cells in models of rat sciatic nerve injury are described, including chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-e-caprolactone), and poly(vinyl alcohol) with conductive materials. The importance of a multidisciplinary approach to tissue engineering the peripheral nerve through development of biomaterials, cell therapies, and preclinical studies is emphasized.
Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development
Carlo Tremolada1 & Valeria Colombo1 & Carlo Ventura2
Abstract Inthepastfewyears,interestinadiposetissueasan ideal source of mesenchymal stem cells (MSCs) has increased. These cells are multipotent and may differentiate in vitro into several cellular lineages, such as adipocytes, chondrocytes, osteoblasts, and myoblasts. In addition, they secrete many bioactive molecules and thus are considered Bmini-drugstores.^ MSCs are being used increasingly for many clinical applications, such as orthopedic, plastic, and reconstructive surgery. Adipose-derived MSCs are routinely obtained enzymatically from fat lipoaspirate as SVF and/or may undergo prolonged ex vivo expansion, with significant senescence and a decrease in multipotency, leading to unsatisfactory clinicalresults.Moreover, these techniquesare hampered by complex regulatory issues. Therefore, an innovative technique (Lipogems®; Lipogems International SpA, Milan, Italy) was developed to obtain microfragmented adipose tissue with an intact stromal vascular niche and MSCs with a high regenerative capacity. The Lipogems® technology, patented in 2010 and clinically available since 2013, is an easyto-use system designed to harvest, process, and inject refined fat tissue and is characterized by optimal handling ability and a great regenerative potential based on adipose-derived MSCs. In this novel technology, the adipose tissue is washed, emulsified, and rinsed and adipose cluster dimensions gradually are reduced to about 0.3 to 0.8 mm. In the resulting
Lipogems® product, pericytes are retained within an intact stromal vascular niche and are ready to interact with the recipient tissue after transplantation, thereby becoming MSCs and starting the regenerative process. Lipogems® has been used in more than 7000 patients worldwide in aesthetic medicineandsurgery,aswellasinorthopedicandgeneralsurgery, with remarkable and promising results and seemingly no drawbacks. Now, several clinical trials are under way to supporttheinitialencouragingoutcomes.Lipogems®technology is emerging as a valid intraoperative system to obtain an optimal final product that may be used immediately for regenerative purposes.
This document summarizes the role of cell-extracellular matrix (ECM) interactions during cancer progression. It discusses how cancer progression involves four stages - initiation, progression, epithelial-mesenchymal transition, and metastasis. During progression, cancer cells undergo changes in adhesion to the ECM and expression of integrin receptors that help the cells survive, grow, and invade at different sites. Modulation of integrin signaling and ECM properties are key for cancer cells to modify their microenvironment and facilitate metastasis.
The potential of using 3D in vitro models for drug efficiency testing compare...Josiah Sim
Three key points:
1) 3D cell cultures provide a more physiologically relevant model than 2D cultures by mimicking the in vivo microenvironment and cell-cell interactions. However, 3D cultures are more complex and expensive.
2) Studies show 3D cultures better maintain tumor dormancy states and drug resistance patterns observed in patients. Ki-67 indexes indicate higher fractions of non-proliferating cells in 3D.
3) While 3D models are improving, they do not fully replicate the in vivo tumor microenvironment and are not yet standardized for high-throughput drug screening. Further development is still needed to address challenges like customizing the microenvironment and expanding models.
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
This document discusses epithelial-mesenchymal transition (EMT) and its role in cancer metastasis. It summarizes findings from a study using a triple-transgenic mouse model of breast cancer metastasis that found: 1) Primary tumor cells disseminated and formed metastases while maintaining their epithelial phenotype, not undergoing EMT. 2) Inhibiting EMT with miR-200 had no effect on metastasis. 3) Non-EMT tumor cells were sensitive to chemotherapy, whereas mesenchymal cells were resistant. The study provides evidence that EMT may not be required for cancer metastasis in this model.
This study investigated the role of mitochondrial dynamics in breast cancer tumorigenesis by examining mitochondrial morphology and cell death in two breast cancer cell lines, HTB-22 and HTB-126, compared to a non-tumorigenic cell line. The study found that HTB-22 cells displayed more mitochondrial fission events compared to HTB-126 cells. HTB-22 cells also showed increased mitophagy but neither cell line exhibited apoptosis. This did not support the hypothesis that breast cancer cells must have elongated mitochondria associated with apoptotic resistance. Future studies will examine apoptotic signaling mechanisms and protein expression following mitochondrial fission in the HTB-22 cell line.
Role of cancer stem cells in cancer therapyniper hyd
This document discusses cancer stem cells (CSCs) and potential therapies targeting them. It begins with introductions to stem cells and CSCs, then covers the history of discovering CSCs. New therapies discussed include targeting CSC-specific markers, signal pathways like Wnt and Notch, CSC metabolism, and epithelial-mesenchymal transition. Clinical trials targeting CSC pathways are also summarized. The document provides an overview of CSCs and recent research into developing treatments focused on these cells.
This document summarizes key topics related to cancer stem cells. It discusses how cancers contain and arise from stem cells, known as cancer stem cells. Traditional cancer therapies target transit amplifying cells but not cancer stem cells. The document outlines several mechanisms of targeting cancer stem cells, including targeting surface markers, inducing apoptosis, and modulating signaling pathways like mTOR, SHH, and WNT/β-catenin. Radiation therapy is also described as damaging cancer cell DNA to kill cells or slow growth. The conclusion emphasizes that identifying therapies targeting cancer stem cells could help prevent cancer recurrence when combined with standard chemotherapy.
This study analyzed a novel Wharton's jelly formulation to quantify growth factors, cytokines, hyaluronic acid, and extracellular vesicles. All samples passed sterility testing. The formulation was found to contain numerous growth factors including IGFBPs and PDGF-AA. It also contained cytokines associated with immunomodulation, wound healing, and regeneration. High levels of hyaluronic acid were detected. Particles in the size range of extracellular vesicles were also present, enclosed by membranes. The study demonstrates that Wharton's jelly contains various regenerative components that may help reduce inflammation and augment healing of musculoskeletal injuries.
REVIEWCancer stem cells a new framework for the designo.docxjoellemurphey
REVIEW
Cancer stem cells: a new framework for the design
of tumor therapies
Boyan K. Garvalov & Till Acker
Received: 14 July 2010 /Revised: 27 August 2010 /Accepted: 16 September 2010
# Springer-Verlag 2010
Abstract Modern tumor therapy has achieved considerable
progress, but many tumors remain refractory to treatment or
relapse following initial remission. Recent evidence points
to one possible reason for this limited therapeutic efficiency:
that the design of anticancer agents so far may not have been
aimed at the right target. While conventional tumor therapies
have targeted the main mass of tumor cells, there is now
compelling evidence that tumor initiation and progression are
driven by a subpopulation of tumor cells that possess stem cell
properties and are resistant to traditional cancer treatments—
the cancer stem cells (CSCs). CSCs have been identified in
most types of cancer and can be separated from the rest of the
tumor cells using appropriate markers. CSCs are regulated by
molecular mechanisms and specific, perivascular, and hypox-
ic microenvironments, which largely overlap with those
controlling stem cells from normal tissues. Our improved
understanding of CSC biology has already provided a number
of novel targets and drug discovery platforms for the design of
specific therapies that aim to eradicate the CSC subpopula-
tion. Therapeutic approaches can be targeted either at
eliminating the CSCs themselves or at disrupting the niches
in which CSCs reside. Moreover, the importance of CSCs for
tumor growth, resistance, and progression implies that clinical
trials and preclinical studies of anticancer therapies should
include as a key element an assessment of the abundance and
persistence of CSCs. Thus, CSC research holds great promise
for providing important new impetus to the fields of tumor
biology and clinical oncology.
Keywords Cancer stem cell . Hypoxia .
Microenvironment . Angiogenesis . Antitumor therapy.
Metastasis
The hierarchy model and cancer stem cells (CSCs)
The classical view of tumor formation is based on the
“stochastic” or “clonal evolution” model [1, 2]. It perceives
the tumor as a mass of hyperproliferative cells with similar
potential for driving tumor growth. Tumor heterogeneity
and progression are seen as the result of variations in the
tumor microenvironment and genetic mutations in individ-
ual cells, followed by selection of those that are best
adapted to support the further growth of the tumor (Fig. 1a).
An alternative concept that has been gaining increasing
experimental support is the “hierarchy” or “cancer stem
cell” model [3]. This model posits that tumors are generated
and maintained in a manner similar to the physiological
stem cell system operating in normal tissues, i.e., by cells
with stem cell-like properties, which self-renew and
differentiate into the distinct cellular subtypes of the tumor
(Fig. 1b). The key novel features of this model are that only
a limited population of tumor cell ...
The document summarizes the process of cancer metastasis through the invasion-metastasis cascade. It involves 6 key steps: 1) Localized invasion of primary tumor cells aided by loss of cell adhesion molecules and matrix metalloproteinases. 2) Intravasation of tumor cells into blood vessels assisted by tumor-associated macrophages. 3) Transport of circulating tumor cells protected by platelet emboli. 4) Extravasation of tumor cells from vessels into distant tissues. 5) Formation of dormant micrometastases. 6) Rare colonization of micrometastases into macroscopic tumors limited by the foreign tissue environment. Metastasis suppressor genes and strategies targeting multiple steps simultaneously show promise for preventing cancer spread.
This literature review finds that umbilical cord tissue, specifically Wharton's jelly, offers the greatest number of harvestable mesenchymal stem cells. The review analyzed 161 studies reporting mesenchymal stem cell yields from various tissue sources, including adipose tissue, bone marrow, umbilical cord tissue, and placental tissue. It found that yields from umbilical cord tissue ranged from 10,000 to 4,700,000 cells per milliliter, far exceeding yields from other sources. Adipose tissue provided the next highest yields, ranging from 4,737 to 1,550,000 cells per milliliter. Bone marrow yields ranged more widely from 1 to 317,400 cells per millil
This document discusses cancer stem cells (CSCs), which are cells that can self-renew and differentiate to produce the heterogeneous cells that comprise a tumor. The stem cell theory of cancer proposes that CSCs, like normal stem cells, sustain cancer growth. CSCs share similarities with normal stem cells such as long lifespans and resistance to apoptosis. Researchers are investigating whether CSCs arise from normal stem cells, progenitor cells, or differentiated cells in adult tissue. While CSCs have been identified in hematopoietic and solid tumors, their discovery has opened new avenues for cancer therapies that target these cells specifically.
Cell within a tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor”.
“CSC can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”.
Mammalian MSC from Selected Species: Features and Applications
Christiane Uder, Sandra Br€uckner, Sandra Winkler, Hans-Michael Tautenhahn,†‡ Bruno Christ†*
Mesenchymal stromal/stem cells (MSC) are promising candidates for cellular therapy of different diseases in humans and in animals. Following the guidelines of the International Society for Cell Therapy, human MSC may be identified by expression of a specific panel of cell surface markers (CD1051, CD731, CD901, CD34-, CD14-, or CD11b-, CD79- or CD19-, HLA-DR-). In addition, multiple differentiation potential into at least the osteogenic, adipogenic, and chondrogenic lineage is a main criterion for MSC definition. Human MSC and MSC of a variety of mammals isolated from different tissues meet these criteria. In addition to the abovementioned, they express many more cell surface markers. Yet, these are not uniquely expressed by MSC. The gross phenotypic appearance like marker expression and differentiation potential is similar albeit not identical for MSC from different tissues and species. Similarly, MSC may feature different biological characteristics depending on the tissue source and the isolation and culture procedures. Their versatile biological qualities comprising immunomodulatory, anti-inflammatory, and proregenerative capacities rely largely on the migratory and secretory capabilities of MSC. They are attracted to sites of tissue lesion and secrete factors to promote self-repair of the injured tissue. This is a big perspective for clinical MSC applications in both veterinary and human medicine. Phase I/II clinical trials have been initiated to assess safety and feasibility of MSC therapies in acute and chronic disease settings. Yet, since the mode of MSC action in a specific disease environment is still unknown at large, it is mandatory to unravel the response of MSC from a given source onto a specific disease environment in suitable animal models prior to clinical applications.
Umbilical cord mesenchymal stem cells (UC-MSCs) show potential advantages over mesenchymal stem cells (MSCs) from other sources for regenerative medicine applications. UC-MSCs display higher proliferation rates and expression of embryonic genes compared to adult MSCs. Transcriptomic analyses indicate UC-MSCs express genes related to development of multiple tissues including bone, liver, cardiovascular and neural systems. While UC-MSCs can differentiate into cell types of multiple lineages, their therapeutic impact is thought to be mainly due to their paracrine effects and immunomodulatory properties. UC-MSCs could have advantages for treating autoimmune and neurodegenerative diseases.
Wharton’s jelly mesenchymal stem cells as off the-shelf cellular therapeutics...raditio ghifiardi
This document discusses Wharton's jelly mesenchymal stem cells (WJMSCs) and their potential as an alternative to bone marrow mesenchymal stem cells (BMMSCs) for regenerative therapies. WJMSCs are isolated from the umbilical cord and have advantages over BMMSCs such as easier accessibility, higher proliferation rates, and greater consistency between samples. Studies show that WJMSCs secrete trophic and immunomodulatory factors that aid tissue repair. However, more research is needed to understand how well WJMSCs can engraft and survive in allogeneic transplant settings and their exact immune modulation mechanisms. The document reviews the immune regulatory properties of WJMSCs
Development of cancer therapeutics is often carried out in 2D cultures prior to testing on animal model. In comparison to 2D cultures, discuss the potential of using 3D in vitro models for drug efficiency testing.
3D In Vitro Models for Drug Efficiency TestingTiffany Ho
3D cell cultures more accurately model the in vivo microenvironment compared to traditional 2D cultures. 3D cultures form cell aggregates or spheroids, mimic tumor development, and allow for more effective drug testing compared to flat monolayers. Emerging technologies like organ-on-chip microfluidic devices and 3D printing have the potential to further advance 3D cell culture models by replicating the functions of human organs and embedding living cells in scaffolds.
This chapter discusses perspectives on employing mesenchymal stem cells from Wharton's jelly of the umbilical cord for peripheral nerve repair. It provides background on regenerative medicine and peripheral nerve injuries. Various biomaterials that have been tested as scaffolds for delivering mesenchymal stem cells in models of rat sciatic nerve injury are described, including chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-e-caprolactone), and poly(vinyl alcohol) with conductive materials. The importance of a multidisciplinary approach to tissue engineering the peripheral nerve through development of biomaterials, cell therapies, and preclinical studies is emphasized.
Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development
Carlo Tremolada1 & Valeria Colombo1 & Carlo Ventura2
Abstract Inthepastfewyears,interestinadiposetissueasan ideal source of mesenchymal stem cells (MSCs) has increased. These cells are multipotent and may differentiate in vitro into several cellular lineages, such as adipocytes, chondrocytes, osteoblasts, and myoblasts. In addition, they secrete many bioactive molecules and thus are considered Bmini-drugstores.^ MSCs are being used increasingly for many clinical applications, such as orthopedic, plastic, and reconstructive surgery. Adipose-derived MSCs are routinely obtained enzymatically from fat lipoaspirate as SVF and/or may undergo prolonged ex vivo expansion, with significant senescence and a decrease in multipotency, leading to unsatisfactory clinicalresults.Moreover, these techniquesare hampered by complex regulatory issues. Therefore, an innovative technique (Lipogems®; Lipogems International SpA, Milan, Italy) was developed to obtain microfragmented adipose tissue with an intact stromal vascular niche and MSCs with a high regenerative capacity. The Lipogems® technology, patented in 2010 and clinically available since 2013, is an easyto-use system designed to harvest, process, and inject refined fat tissue and is characterized by optimal handling ability and a great regenerative potential based on adipose-derived MSCs. In this novel technology, the adipose tissue is washed, emulsified, and rinsed and adipose cluster dimensions gradually are reduced to about 0.3 to 0.8 mm. In the resulting
Lipogems® product, pericytes are retained within an intact stromal vascular niche and are ready to interact with the recipient tissue after transplantation, thereby becoming MSCs and starting the regenerative process. Lipogems® has been used in more than 7000 patients worldwide in aesthetic medicineandsurgery,aswellasinorthopedicandgeneralsurgery, with remarkable and promising results and seemingly no drawbacks. Now, several clinical trials are under way to supporttheinitialencouragingoutcomes.Lipogems®technology is emerging as a valid intraoperative system to obtain an optimal final product that may be used immediately for regenerative purposes.
This document summarizes the role of cell-extracellular matrix (ECM) interactions during cancer progression. It discusses how cancer progression involves four stages - initiation, progression, epithelial-mesenchymal transition, and metastasis. During progression, cancer cells undergo changes in adhesion to the ECM and expression of integrin receptors that help the cells survive, grow, and invade at different sites. Modulation of integrin signaling and ECM properties are key for cancer cells to modify their microenvironment and facilitate metastasis.
The potential of using 3D in vitro models for drug efficiency testing compare...Josiah Sim
Three key points:
1) 3D cell cultures provide a more physiologically relevant model than 2D cultures by mimicking the in vivo microenvironment and cell-cell interactions. However, 3D cultures are more complex and expensive.
2) Studies show 3D cultures better maintain tumor dormancy states and drug resistance patterns observed in patients. Ki-67 indexes indicate higher fractions of non-proliferating cells in 3D.
3) While 3D models are improving, they do not fully replicate the in vivo tumor microenvironment and are not yet standardized for high-throughput drug screening. Further development is still needed to address challenges like customizing the microenvironment and expanding models.
A normal cell can be transformed into a cancerous cell. Discuss the therapeutic strategies that are employed to target the cellular transformation process for cancer prevention and treatment.
This document discusses epithelial-mesenchymal transition (EMT) and its role in cancer metastasis. It summarizes findings from a study using a triple-transgenic mouse model of breast cancer metastasis that found: 1) Primary tumor cells disseminated and formed metastases while maintaining their epithelial phenotype, not undergoing EMT. 2) Inhibiting EMT with miR-200 had no effect on metastasis. 3) Non-EMT tumor cells were sensitive to chemotherapy, whereas mesenchymal cells were resistant. The study provides evidence that EMT may not be required for cancer metastasis in this model.
This study investigated the role of mitochondrial dynamics in breast cancer tumorigenesis by examining mitochondrial morphology and cell death in two breast cancer cell lines, HTB-22 and HTB-126, compared to a non-tumorigenic cell line. The study found that HTB-22 cells displayed more mitochondrial fission events compared to HTB-126 cells. HTB-22 cells also showed increased mitophagy but neither cell line exhibited apoptosis. This did not support the hypothesis that breast cancer cells must have elongated mitochondria associated with apoptotic resistance. Future studies will examine apoptotic signaling mechanisms and protein expression following mitochondrial fission in the HTB-22 cell line.
Role of cancer stem cells in cancer therapyniper hyd
This document discusses cancer stem cells (CSCs) and potential therapies targeting them. It begins with introductions to stem cells and CSCs, then covers the history of discovering CSCs. New therapies discussed include targeting CSC-specific markers, signal pathways like Wnt and Notch, CSC metabolism, and epithelial-mesenchymal transition. Clinical trials targeting CSC pathways are also summarized. The document provides an overview of CSCs and recent research into developing treatments focused on these cells.
This document summarizes key topics related to cancer stem cells. It discusses how cancers contain and arise from stem cells, known as cancer stem cells. Traditional cancer therapies target transit amplifying cells but not cancer stem cells. The document outlines several mechanisms of targeting cancer stem cells, including targeting surface markers, inducing apoptosis, and modulating signaling pathways like mTOR, SHH, and WNT/β-catenin. Radiation therapy is also described as damaging cancer cell DNA to kill cells or slow growth. The conclusion emphasizes that identifying therapies targeting cancer stem cells could help prevent cancer recurrence when combined with standard chemotherapy.
This study analyzed a novel Wharton's jelly formulation to quantify growth factors, cytokines, hyaluronic acid, and extracellular vesicles. All samples passed sterility testing. The formulation was found to contain numerous growth factors including IGFBPs and PDGF-AA. It also contained cytokines associated with immunomodulation, wound healing, and regeneration. High levels of hyaluronic acid were detected. Particles in the size range of extracellular vesicles were also present, enclosed by membranes. The study demonstrates that Wharton's jelly contains various regenerative components that may help reduce inflammation and augment healing of musculoskeletal injuries.
REVIEWCancer stem cells a new framework for the designo.docxjoellemurphey
REVIEW
Cancer stem cells: a new framework for the design
of tumor therapies
Boyan K. Garvalov & Till Acker
Received: 14 July 2010 /Revised: 27 August 2010 /Accepted: 16 September 2010
# Springer-Verlag 2010
Abstract Modern tumor therapy has achieved considerable
progress, but many tumors remain refractory to treatment or
relapse following initial remission. Recent evidence points
to one possible reason for this limited therapeutic efficiency:
that the design of anticancer agents so far may not have been
aimed at the right target. While conventional tumor therapies
have targeted the main mass of tumor cells, there is now
compelling evidence that tumor initiation and progression are
driven by a subpopulation of tumor cells that possess stem cell
properties and are resistant to traditional cancer treatments—
the cancer stem cells (CSCs). CSCs have been identified in
most types of cancer and can be separated from the rest of the
tumor cells using appropriate markers. CSCs are regulated by
molecular mechanisms and specific, perivascular, and hypox-
ic microenvironments, which largely overlap with those
controlling stem cells from normal tissues. Our improved
understanding of CSC biology has already provided a number
of novel targets and drug discovery platforms for the design of
specific therapies that aim to eradicate the CSC subpopula-
tion. Therapeutic approaches can be targeted either at
eliminating the CSCs themselves or at disrupting the niches
in which CSCs reside. Moreover, the importance of CSCs for
tumor growth, resistance, and progression implies that clinical
trials and preclinical studies of anticancer therapies should
include as a key element an assessment of the abundance and
persistence of CSCs. Thus, CSC research holds great promise
for providing important new impetus to the fields of tumor
biology and clinical oncology.
Keywords Cancer stem cell . Hypoxia .
Microenvironment . Angiogenesis . Antitumor therapy.
Metastasis
The hierarchy model and cancer stem cells (CSCs)
The classical view of tumor formation is based on the
“stochastic” or “clonal evolution” model [1, 2]. It perceives
the tumor as a mass of hyperproliferative cells with similar
potential for driving tumor growth. Tumor heterogeneity
and progression are seen as the result of variations in the
tumor microenvironment and genetic mutations in individ-
ual cells, followed by selection of those that are best
adapted to support the further growth of the tumor (Fig. 1a).
An alternative concept that has been gaining increasing
experimental support is the “hierarchy” or “cancer stem
cell” model [3]. This model posits that tumors are generated
and maintained in a manner similar to the physiological
stem cell system operating in normal tissues, i.e., by cells
with stem cell-like properties, which self-renew and
differentiate into the distinct cellular subtypes of the tumor
(Fig. 1b). The key novel features of this model are that only
a limited population of tumor cell ...
The document summarizes the process of cancer metastasis through the invasion-metastasis cascade. It involves 6 key steps: 1) Localized invasion of primary tumor cells aided by loss of cell adhesion molecules and matrix metalloproteinases. 2) Intravasation of tumor cells into blood vessels assisted by tumor-associated macrophages. 3) Transport of circulating tumor cells protected by platelet emboli. 4) Extravasation of tumor cells from vessels into distant tissues. 5) Formation of dormant micrometastases. 6) Rare colonization of micrometastases into macroscopic tumors limited by the foreign tissue environment. Metastasis suppressor genes and strategies targeting multiple steps simultaneously show promise for preventing cancer spread.
International Journal of Stem Cell Research and Transplantation (IJST) is an international, Open Access, peer-reviewed journal, which mainly focuses, on the advancements made in the field of cell biology, specifically in the field of Stem Cells.
International Journal of Stem Cell Research and Transplantation (IJST) is a peer-reviewed journal, and is dedicated to providing information with respect to the latest advancements that are being upgraded in our everyday life with respect to the application of Stem cells.
International Journal of Stem Cell Research and Transplantation (IJST) ISSN:2328-3548, is a free, Open Access, Peer-reviewed, exclusive online journal covering areas of Stem cell research, translational work and Clinical studies in the specialty of Stem Cells and Transplantation including allied specialties relevant to the core subject, which is dedicated in publishing high quality manuscripts.
describe two recent scientific research studies and it therapies inv.pdffeelingcomputors
describe two recent scientific research studies and it therapies involving stem cells. Explain what
the researches did(how the study was performed).the result and conclusion
Solution
Therapies for wound healing:
Wound healing is a dynamic process bleeding and coagulation, acute inflammation, cell
migration, proliferation, differentiation, angiogenesis, re-epithelialization, and synthesis and
remodeling of the extracellular matrix. Many local and systemic factors can impair wound
healing process resulting in prolonged and non-healing chronic wounds which affects the quality
of patients’life. Stem cell-based therapy represents a promising therapeutic approach for wound
healing. Stem cells have been shown to mobilize and find home for ischemic and wounded
tissues where they secrete chemokines and growth factors to promote angiogenesis and
extracellular matrix remodeling.
In wounds, It has been reported that Mesenchymal stem cells are recruited to wound skin at the
time of wound healing and have the capacity to differentiate into multiple skin cell types
including keratinocytes, endothelial cells and pericytes. Furthermore, circulating MSC
recruitment was induced by a specific chemokine (SLC/CCL21)/chemokine receptor (CCR7)
interaction both in vitro and in vivo. Intradermal injection of SLC/CCL21 significantly
accelerated wound closure by increasing rates of MSC accumulation, especially the formation of
endothelial transdifferentiated cells (Sasaki et al., 2008) . MSCs are good candidate which can be
transdifferentiated into endothelial cells and epithelial- fibroblast cells for wound repair therapy
and understanding there signaling mechanism can further help in regenerative medicine.
Mesenchymal stem cells (MSC), referred as mesenchymal stromal cells , colony forming unit-
fibroblasts and mesenchymal progenitor cells , were first identified by Friedenstein as
subpopulation of bone marrow cells. Other than hemopoietic stem cells and differentiated
lineages, bone marrow contains a subset of nonhemopoietic cells, mesenchymal stem cells
(MSCs) that account for roughly 0.01–0.001% of the bone marrow derived cell population .
These are a rare population of non-hematopoietic stromal cells, present in the bone marrow and
most connective tissues of the body.They have capability to proliferate in vitro in uncommitted
state and retain their multilineage differentiation potency which make them attractive candidates
for biological cell-based tissue repair approaches. These cells have ability to differentiate into
three mesenchymal lineages: adipogenic , osteogenic, chondrogenic and can be induced to
commit to various other phenotypes like neurogenic, hepatocytes,myogenic, tenocytes,
cardiomyocytes, fibroblast and endothelial cells. In vivo studies have also shown that MSCs can
differentiate into tissue-specific cells in response to cues provided by different organs . In
addition to pluripotency, MSCs are known to have immunosuppressive effects involving vari.
Give background information concerning EMT and include what is known.pdfrozakashif85
Give background information concerning EMT and include what is known about EMT in normal
development as well as in neoplasms. What are strategies that could be used to overcome drug
resistance in cancer cells by targeting EMT (minimum four paragraphs).
Solution
Answer:
Cancer stem cell (CSC) hypothesis: This hypothesis elucidating that the CSC are the
subpopulation and able to exert higher resistance associated with explicit capability to self-renew
finally to differentiate into different offspring of cancer cells to generate a tumor. This
hypothesis is based on the cellular mechanisms exclusively developed inside the CSC to exert
resistance such pathways are mainly through Wnt signaling, Notch signaling. There are other
targets to regulate proliferation and differentiation through ABC transporter system and receptor
tyrosine kinases. These targets are the future stem cells anti-cancer therapies in regulating the
proliferation & differentiation of cancer cells as CSCs have a potential relationship with
epithelial-mesenchymal transition (EMT).
Metastasis has many steps. The main cancer cell morphological features that support invasion,
intravasation, and extravasation are epithelial-mesenchymal transition via cell -adhesion
molecules. Invasion is mainly due to presence of cell adhesion molecules such as integrins on the
cancer cells finally promote the movement of cancer cells to another region. This process is
going to connect adjacent cells to tumor cells finally undergo epithelial-mesenchymal transition
(EMT) result in formation of \"continuously dividing neoplasms\" with higher drug resistence to
cure compared to normal cells
Strategies that could be used to overcome drug resistance in cancer cells by targeting EMT:
\"A combination therapy of neutraceuticals & chemotherapeutic agents\" are most promising
strategies to overcome drug resistance in cancer cells by targeting EMTs, cancer stem cells
(CSC) &
Modulation of microRNAs do promote effective strategy to overcome drug resistance in cancer
cells
Oligonucletodie deliver: Another strategy could be used to overcome drug resistance in cancer
cells by targeting EMT. In this method, synthesized microRNAs are going to make in the form of
\"nanoparticle or microsomal\" formulation finally used to target microRNAs in cancer cells
result in \"complete destruction of pre-mRNA\" finally there will no translation mechanism to
synthesize \"cell survival proteins\" to proliferate.
This review article discusses the application of nanoscaffolds in mesenchymal stem cell-based therapy. It begins with an introduction about the need for regenerative medicine as an alternative to organ transplantation due to donor shortages. It describes mesenchymal stem cells and nanofibers/scaffolds as two essential components in regenerative medicine. Recently, the combination of mesenchymal stem cells and nanofibers/scaffolds has been utilized to obtain more homogeneous stem cell populations with higher proliferation rates and differentiation potential, which are important for regenerative medicine. The review then discusses topics such as the biology, sources, characterization, and isolation of mesenchymal stem cells. It also covers the
Cytokine Immunotherapy: A Forthcoming Visible Feature in Cancer TherapeuticsSachin K. S. Chauhan
The document discusses cytokine immunotherapy as a promising approach for cancer treatment. It notes that cytokines can stimulate the immune system to fight tumors, but that mono-cytokine therapy has limitations. Combined cytokine therapy or cytokine therapy combined with other treatments may be more effective by creating a specific immune response. The document advocates focusing research on combination therapies to help overcome drawbacks of traditional cancer treatments.
In vitro models are crucial tools in cancer research because they assist researchers to identify carcinogens, developing cancer therapies, drug discovery, and study about the molecular pathways of tumour growth and spread. Cancer cells are an essential part of any in vitro tumour model. Cancer cell lines are simple to culture, allow for quick comparisons of experiments, and are commonly employed to research tumour cell biology molecular pathways. Tumour cell biology, 3D cell culture, tissue engineering, biomaterials, microfabrication, and microfluidics advancements have facilitated the dynamic development of in vitro tumour models.
In vitro models are crucial tools in cancer research because they assist researchers to identify carcinogens, developing cancer therapies, drug discovery, and study about the molecular pathways of tumour growth and spread. Cancer cells are an essential part of any in vitro tumour model.
This document summarizes research optimizing the transfection of umbilical cord mesenchymal stem cells (UC-MSCs) with minicircle plasmid DNA using Lipofectamine LTX. The researchers tested different ratios of plasmid to Lipofectamine LTX, volumes of transfection complexes, cell densities, and presence or absence of medium. They found that a 1:2 ratio of 3μg plasmid to 6μl Lipofectamine LTX, transfecting 50,000 cells with 150μl of the transfection complex in the presence of medium, resulted in the highest expression of the GFP reporter gene as observed by fluorescence microscopy 72 hours after transfection. Flow cytometry was also used to quantitatively measure transfection efficiency
This document summarizes the role of stem cells in breast cancer. It discusses how mammary stem cells can act as sites for breast cancer initiation due to their long lifespan and ability to accumulate mutations. Cancer stem cells make up a small fraction of tumor cells but are important for tumor progression and metastasis. These cancer stem cells are resistant to chemotherapy and radiation therapy due to elevated expression of drug efflux pumps and anti-apoptotic proteins. The document reviews markers that are used to identify breast cancer stem cells, such as CD44, CD24, and ALDH1. Targeting these cancer stem cells may be important for overcoming drug resistance in breast cancer treatment.
Cancer stem cells (CSCs) are rare cancer cells that have properties similar to normal stem cells, allowing them to both self-renew and differentiate into the other cell types that make up a tumor. CSCs are thought to drive tumor growth and relapse after treatment. The first evidence of CSCs came from studies in 1997 that isolated a subpopulation of leukemia cells capable of initiating new tumors. Since then, CSCs have been identified in several other cancer types based on their ability to form tumors from very few cells in animal models. CSCs may explain why conventional cancer treatments fail to cure cancers by mainly targeting differentiated cells rather than the tumor-initiating CSCs.
CHI's Targeting Stromal Cells in Cancer and Inflammatory Diseases Conference ...James Prudhomme
This virtual meeting will highlight cutting-edge science and provide insight into recent developments towards therapeutic stromal cell targeting in cancer and chronic inflammatory diseases. View full details and register: https://www.healthtech.com/stroma-conference
TUMOR MICROENVIORNMENT IN HEAD AND NECK CANCER.pptxRhythmKarir
The document summarizes research on the effect of the tumor microenvironment on head and neck cancer. It finds that the microenvironment, composed of cells like cancer-associated fibroblasts and tumor-associated macrophages, plays a key role in tumor progression by modifying the environment to support cancer cell growth, invasion, and metastasis. While past research focused on genetic changes in cancer cells, current evidence indicates the microenvironment contributes substantially to head and neck cancer development and differences in the microenvironment may help explain variations in therapeutic responses.
Cancer Stem Cells and the Unicellular Life Cycle of Cancer_Crimson PublishersCrimsonpublishersCancer
All eukaryotes, from protists to mammalians, preserve a unicellular life cycle inherited from the common ancestor that can be reactivated under unfavorable living conditions. The cell-of-origin of cancer escapes its death by forming a protected polyploid cyst-like structure (CLS), that starts the unicellular life cycle of cancer. The reversal to unicellularity occurs through genomic and epigenetic alterations that activate the MUT switch of early Metazoans and not through mutations. The microcell progeny of CLSs spread into tissues and organs and form the CSC pool of aCLS cancers. Depending on the environment, the CSC pool differentiates a reproductive cell subline, which forms new aCLSs by cyclic encystment and asymmetric cell division, or a somatic subline, which proliferates strongly by symmetric cell division without cyst differentiation.
Cancer stem cells &new therapeutics methodsmahdi hatami
This document discusses cancer stem cells (CSCs) and new therapeutic approaches to target them. It introduces CSCs, their characteristics like self-renewal and chemoresistance. CSCs can be identified by specific cell surface markers and sphere formation assays. New therapies aim to target CSCs' signaling pathways, surface markers, drug efflux pumps, and microenvironment. Targeting CSCs provides a promising approach for improving cancer treatment outcomes as CSCs are responsible for tumor growth, metastasis, and therapeutic resistance.
Mesenchymal stem cells (MSCs) show potential in treating various orthopaedic conditions. MSCs can differentiate into bone, cartilage, and other tissues, helping repair fractures and cartilage/meniscus injuries. They also secrete factors that promote angiogenesis, regulate inflammation, and induce tissue regeneration through paracrine effects. Clinical studies show MSCs may effectively treat non-union fractures, osteoarthritis, and femoral head necrosis by differentiating into local tissues or secreting factors that aid repair. However, larger high-quality studies are still needed to confirm efficacy, especially for late-stage conditions.
Similar to International Journal of Stem Cells & Research (20)
A 5-year old boy, with an established diagnosis of a topic
dermatitis, previously treated by topical corticosteroids and emollient cream with a good improvement, developed widespread papules on his legs, hands and forearm that appeared 5 months ago.
Methods: Retrospectively, the file records of the patients who underwent sleeve gastrectomy were examined. Demographic features, Body Mass Index (BMI), the mouth opening, Mallampati score, thyromental distance, sternomental distance, neck circumference measurements and videolaryngoscopic examination results were recorded Results: In a total of 140 consecutive patients (58 male, 82 female) were included in the study. The mean age of the study participants was 35.40 ± 9.78 and the mean BMI of the patients was 44.33 ± 7.52 kg/m2
. The mean mouth opening of the patients was 4.82 ± 0.54 cm
and the mean neck circumference was 43.52 ± 4.66 cm. The mean thyromental distance was 8.02 ± 1.00 cm and the mean sternomental distance was16.58 ± 1.53 cm. Difficult intubation was determined in 8 (5.7%) patients. In logistic regression analysis, age (p : 0.446), gender (p : 0.371), BMI (p : 0.947), snoring (p : 0.567), sleep apnea (p : 0.218), mouth opening (p : 0.687), thyromental distance (p :0.557), sternomental (p : 0.596) and neck circumference (p : 0.838) were not the independent predictors of difficult intubation. However, Mallampati score (p : 0.001) and preoperative direct laryngoscopy findings (p : 0.037) performed in outpatient clinic were the significant
predictors of difficult intubation. Interestingly, all patients with grade 4 laryngoscopy findings had difficult intubation.
Introduction: Laparoscopic surgery has been performed in Mexico since 1989, but no reports about training tendencies exist. We conducted a national survey in 2015, and here we report the results concerning training characteristics during the surgical residence of the respondents. Materials and Methods: A prospective study was conducted through a survey questioning demographic data, laparoscopic training during pre and post surgical residency and other of areas of laparoscopic practice. The sample was calculated and survey piloted before
application. Special interest in this report was placed on type and quality of training received. Data are reported in percentages.
Heterotopic Ossification (HO) is defined as pathological bone formation at locations where bone normally does not exist. The
presence of HO has been found to be a rare complication after stroke in several studies, whereas there are only sporadic references relating HO to Cerebral Palsy (CP) and few for CP and stroke. No effective treatment for HO has yet been found, whereas the cellular and molecular mechanisms have not been completely understood. Therefore, increased awareness among physicians is required, as a challenge for early diagnosis and treatment. A case of a male patient with CP, who developed HO on the paretichip joint following an ischemic stroke is presented.
Objectives: To assess the practice of food hygiene and safety, and its associated factors among street food vendors in urban areas of Shashemane, West Arsi Zone, Oromia Ethiopia, 2019.
Methods: Cross-sectional study design was applied from December 28, 2019 to January 27, 2020. Data was collected from 120 food handlers, which were selected by purposive sampling techniques. Information was gathered from interview and field observation by conducting food safety survey and using questionnaires via face to face interview. The collected data was entered using Epi Data 3.1 and finally, it was analyzed using SPSS VERSION 20.
A Division I football player experienced acute posterior leg pain while playing. An ultrasound examination revealed an unusual injury - a complete rupture of the plantaris tendon mid-substance. This type of isolated plantaris tendon injury has rarely been reported. Ultrasound was useful for diagnosis and guided rehabilitation by monitoring healing over time. The athlete was able to return to full competition within 3 weeks through a progressive rehabilitation program focused on restoring range of motion and strength. This case suggests isolated plantaris tendon injuries may allow for faster return to play than other potential causes of posterior leg pain.
Type 1 Diabetes (T1D), is a severe disease, representing 5-10% of all reported cases of diabetes worldwide. Fulminant Type 1 Diabetes Mellitus (FT1D) is a subtype of type 1 diabetes mellitus that is largely characterized by the abrupt onset of Diabetic Ketoacidosis (DKA) and severe hyperglycemia without insulin defi ciency. Viral infections have been hypothesized to play a major role in the pathogenesis of Fulminant Type 1 Diabetes Mellitus (FT1D) through the complete and rapid destruction of pancreatic beta cells. Coxsackie viral infection has been detected in islets of 50% of the pancreatic tissue recovered from recent-onset Type 1 Diabetes (T1D) patients. In this report we have highlighted a case where the patient developed a Group B Coxsackie virus infection culminating in the development of Fulminant Type 1 Diabetes Mellitus (FT1D).
Methods: Cercariae are released by infected water snails. To determine the occurrence of cercariae-emitting snails in SchleswigHolstein, 155 public bathing places were visited and searched for fresh water snails. Family and genus of the collected snails were determined and the snails were examined for the shedding of cercariae, using a standard method and a newly developed method.
Objective: To generate preliminary information about of enteroviruses and Enterovirus 71 (EV71) in patients with aseptic meningitis in Khartoum State, Sudan.
Method: Cerebrospinal fluid specimens were collected from 89 aseptic meningitis patients from different Khartoum Hospitals
(Mohammed Alamin Hamid Hospital, Soba Teaching Hospital, Omdurman Military Hospital, Alban Gadeed Teaching Hospital and Police Hospital) within February to May 2015. Among these 89 patients, 43 (48%) were males and 46 (52%) were females. The patient’s age ranged between 1 day and 30 years old. The collected specimens were assayed to detect enteroviruses and EV71 RNA using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique
Femoral hernias, comprise 2% to 4% of all hernias in the inguinal region, and occur most commonly in women. Th ey present typically with a mass below the level of the inguinal ligament. The sac may contain preperitoneal fat, omentum, small bowel, or other structures and have a high rate of incarceration and strangulation due to the small size of the hernia neck orifice, requiring emergency surgery. We present the case of a 54-year-old female patient with intestinal occlusion due to incarcerated femoral hernia, repaired by laparoscopic approach, that gave the patient the opportunity to attend her daughter’s wedding the same day.
Small Supernumerary Marker Chromosome (sSMC) is a rare genetic condition marked by the presence of an extra chromosome to the 46 human chromosomes. This case report describes a 4 year old child with SSMC on the 46th chromosome. The child presented with delayed speech and language development, seizures and mild developmental delay. Speech and Language evaluation was carried out and management options are discussed.
A catheter is a thin tube made from medical grade materials that serve a broad range of functions, but mainly catheters are medical devices that can be inserted in the body to treat disease or perform surgical procedures. Catheters have been inserted into body cavities, ducts, or vessels to allow for drainage, administration of therapeutic fluids or gases, operational access for surgery. Catheters help perform tasks in various systems such as cardiovascular, urological, gastrointestinal, neurovascular, and ophthalmic systems. A dataset of 12 patients with varying “weights” and “heights” was recorded along with the lengths of their catheter tubes. This data set was found from two revered statistical textbooks on linear regression and the Department of Scientific Computing at Florida State University. This data set was not able to be linked to any particular clinical or experimental research studies, but the data set can be used to help catheter manufacturers and medical professionals better decide on what particular catheter lengths to use for patients knowing only their height & weight. These research insights could be helpful to healthcare professionals that have patients with incomplete or no healthcare records
to decide what catheter length to use. The main investigative inquiry that needed to be answered was how does patient weight & height influence catheter length together and separately? We conducted linear regression and other statistical analysis procedures in R program & Microsoft Excel and discovered that this data exhibited a quality called multi collinearity. With multi collinearity, all predictors (2 or more
independent variables) are not significant in an all encompassing linear aggression, but the predictors might be significant in their own individual linear regressions. Individual linear regression analyses were conducted for both patient height & weight to see how much they both contribute to varying catheter length. Patient weight was found to be more impatful than patient height in relationship to catheter length, even though height and weight are a classical example of multi collinearity predictors.
Bovine mastitis has a negative impact through economic losses in the dairy sector across the globe. A cross sectional study was carried out from September 2015 to July 2016 to determine the prevalence of bovine mastitis, associated risk factors and isolation of major causative bacteria in lactating dairy cows in selected districts of central highland of Ethiopia. A total of 304 lactating cows selected randomly from five districts were screened by California Mastitis Test (CMT) for subclinical mastitis. Based on CMT result and clinical examination, over all prevalence of mastitis at cow level was 70.62% (214/304).
Two hundred fourteen milk samples collected from CMT positive cows were cultured for isolation of major causative bacteria. From 214 milk samples,187 were culture positive and the most prevalent isolates were Staphylococcus aureus 42.25% (79/187) followed by Streptococcus agalactiae 14.43%
(27/187). Other bacterial isolates were included Coagulase Negative Staphylococcus species 12.83% (24/187), Streptococcus dysgalactiae 5.88% (11/187), Escherichia coli 13.38% (25/187) and Entrococcus feacalis 11.23% (21/187) were also isolated. Moreover, age, parity number, visible teat abnormalities,husbandry practice, barn fl oor status and milking hygiene were considered as risk factors for the occurrence of bovine mastitis and they were found significantly associated with the occurrence of mastitis (p < 0.05). The findings of this study warrants the need for strategic approach including dairy extension that focus on enhancing dairy farmers’ awareness and practice of hygienic milking, regular screening for subclinical mastitis, dry cow therapy and culling of chronically infected cows.
A 36-year-old female developed right upper quadrant pain and nausea after taking the herbal supplement kratom for two weeks to manage back pain. Laboratory tests showed elevated liver enzymes. A liver biopsy ruled out other causes and determined she had drug-induced liver injury from kratom use. Her symptoms and liver enzymes gradually returned to normal over six weeks after stopping kratom. The case report discusses kratom's potential for hepatotoxicity and advises clinicians to consider its effects on patient health.
The assessment, diagnosis and treatment of critically ill patients is extremely challenging. Patients often deteriorate whilst being
reviewed and their rapidly changing pathophysiology barrages healthcare professionals with new data. Furthermore, comprehensive assessments must be postponed until the patient has been stabilised. So, important data and interventions are often missed in the heat of the moment. In emergency situations, suboptimal management decisions may cause signifi cant morbidity and mortality. Fortunately, standardisation and careful design of documentation (i.e. proformas and checklists) can enhance patient safety. So, I have developed a series of checklist proformas to guide the assessment of critically ill patients. These proformas also promote the systematic recording and presentation of information to facilitate the retrieval of the precise data required for the management for critically ill patients. The proformas have been modifi ed extensively over the last twenty years based on my personal experience and extensive consultation with colleagues in several world-renowned centres of excellence. The proformas were originally developed for use in the intensive therapy unit
or high dependency unit. However, they have been adapted for use by outreach teams reviewing patients admitted outside of critical care areas. The use of these tools can direct eff orts to provide appropriate organ support and provides a framework for diagnostic reasoning.
This review article discusses microvascular and macrovascular disease in systemic hypertension. It summarizes that:
1) Cardiac imaging plays a crucial role in risk stratifying hypertensive patients and identifying management strategies by properly diagnosing microvascular and coronary artery disease.
2) The nitric oxide synthase (eNOS) G298 gene allele may be a marker for microvascular angina in hypertensive patients, as studies have found it to be more prevalent in hypertensive patients with chest pain and reversible myocardial defects but normal coronary arteries.
3) Both structural changes like capillary rarefaction and functional changes like endothelial dysfunction can cause microvascular dysfunction and angina in hypertensive individuals in the absence of
This study characterized dengue infections in Pakistan by analyzing hematological and serological markers in 154 suspected dengue cases and 146 control patients with other febrile illnesses. NS1 antigen was detected in 55% of dengue cases, IgM antibodies in 30%, and both in 15%. Control groups primarily had malaria (71%) and enteric fever (20%). Hematological markers (platelet count, hematocrit, WBC) measured before and after treatment showed significant differences for platelet count and hematocrit but not WBC count between the groups. Analysis of clinical symptoms and serological/hematological markers helps diagnose dengue, assess prognosis, and inform prevention efforts to reduce morbidity, mortality and spread of the disease.
Researchers from Utrecht recently published yet another paper on the use of Magnetic Resonance Imaging (MRI)demonstrating an additional failed attempt to understand the importance of qualitative versus quantitative imaging, and anatomic versus physiologic imaging. Th e implications of this failure here cannot be overstated.
Introduction: Stroke is an even more dramatic major public health problem in young people. Goal of the study: Contribute to the knowledge of strokes in young people. Methodology: This was a retrospective study carried out over a period of 02 years (January 2017 to December 2018) including the files of patients aged 18 to 49 years hospitalized for any suspected case of stroke in the Neurology department of the University Hospital
Center of the Sino-Central African Friendship (CHUSCA) of Bangui.
Background: This report describes a unique case of a patient that developed psychotic symptoms believed to be secondary
to a tentorial meningioma with associated hydrocephalus. These psychotic symptoms subsequently abated with placement of a
ventriculoperitoneal shunt. Case description: 60-year-old female was admitted to an inpatient psychiatric facility on a psychiatric involuntary commitment petition due to progressive paranoia, homicidal ideation and psychosis. The work up showed a calcified six cm tentorial meningioma with associated hydrocephalus. The patient initially rejected treatment but later became amenable to placement of Ventriculoperitoneal Shunt
(VPS).
More from SciRes Literature LLC. | Open Access Journals (20)
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
After getting it read you will definitely understand the topic.
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)MuskanShingari
Statistics- Statistics is the science of collecting, organizing, presenting, analyzing and interpreting numerical data to assist in making more effective decisions.
A statistics is a measure which is used to estimate the population parameter
Parameters-It is used to describe the properties of an entire population.
Examples-Measures of central tendency Dispersion, Variance, Standard Deviation (SD), Absolute Error, Mean Absolute Error (MAE), Eigen Value
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. SCIRES Literature - Volume 3 Issue 1 - www.scireslit.com Page - 008
International Journal of Stem Cells & Research
INTRODUCTION
Mesenchymal Stem Cells (MSCs) have distinct characteristics
and they can undergo self-renewing divisions as well as give rise to
progenitor cells. They are multipotent and can be obtained mainly
from bone marrow and adipose tissue. MSCs have the ability to
differentiate into diverse tissue types of other lineages within or across
germ lines including the mesodermal lineage, such as adipocytes,
osteocytes, chondrocytes and cells of other embryonic lineages like
glial cells [1]. They secrete several paracrine factors including chemo-
attractants for endothelial lineage cells, monocytes, and macrophages,
as well as inflammatory factors such as various chemokines and
interleukins. Through chemokine signaling, MSCs interact with the
extracellular matrix that results in the transcriptional activation of
target genes in cancer cells as well as macrophages and lymphocytes.
One of the main characteristics of hMSCs is their homing abilities
to the primary tumor site and metastatic sites. Chemokines and their
receptors were proposed to be involved in hMSC migration and
homing [2,3]. Moreover, recent studies have shown that hMSCs have
antiapoptotic characteristics Yang, et al. [4] in Bone Marrow-derived
MSCs (BM-MSCs), which decrease oxidative stress, apoptosis and
hippocampal damage in the brain [5]. Similar to the BM-MSCs,
MSC-derived exosomes were shown to have similar functions in
suppressing and repairing inflammatory responses which lead to
tissue damage and modulating the immune system, however, these
findings remain to be controversial [6].
MSCs may interact with tumor cells to promote tumor growth
directly or indirectly through autocrine/paracrine mechanisms.
MSCs are considered to be the source of Tumor-Associated
Fibroblasts (TAFs), which are important components of tumor
stroma. Therefore, MSCs play an important role in orchestrating the
tumor microenvironment through angiogenesis and modulation of
both immune system and tumor stromal architecture [7]. It is possible
that MSCs provide a specific microenvironment or a niche for cancer
stem cells. Therefore, investigating the interaction between stem cells
and their specific microenvironment/niche cells will enhance the
understanding of cancer development, especially metastasis [7-11].
Several studies including animal models and pre-clinical
investigations report using MSCs in cancer treatments. Although
BM-MSCs are the most common choice in these studies, they are not
very practical, since harvesting bone marrow is an invasive procedure
and it yields a small number of cells. Besides, the differentiation
potential and the lifespan of BM-MSCs decrease with the advanced
donor’s age [11-16].
Although BM-MSCs is the gold standard for the in-vitro
experiments as well as clinical applications Batsali, et al. [17], other
alternative sources of MSCs, such as adipose tissue and umbilical cord
blood, have gained more importance in the recent years. Adipose
tissue-derived MSCs are obtained from the subcutaneous tissue.
They have similar expansion potential, differentiation capacity, and
MSC immunophenotype as the MSCs derived from the bone marrow
[14]. Umbilical cord, obtained after the removal of placenta, is rich
in hematopoietic stem cells [18,19]. One of the differences between
the MSCs obtained from bone marrow and umbilical cord is that
umbilical cord-derived MSCs have a higher expansion rate compared
to both bone marrow and adipose tissue-derived MSCs [14,20] that
could be due to the higher telomerase activity of the umbilical cord-
derived MSCs [21].
Therapeutic use of hMSCs in cancer therapy
To date, cancer therapy is still one of the most challenging
treatments. One reason is that cancer has a dysregulated cellular
self-renewal capacity. Gene and viral cancer therapies have
shown improved outcomes, however, there is still a great need for
development. Cancer therapy directed at tumor cells is very difficult.
However,thefundamentalissueincancerresearchistheidentification
of the cell type capable of sustaining the outgrowth of the neoplastic
clone within solid tumors. Therefore therapies specifically directed at
the cancer stem cells have gained importance to reduce and stop the
metastatic tumors. Recent studies have shown that use of stem cells
obtained from adult the tissue may be a novel vehicle for stem cell-
mediated cancer therapy with improved anti-tumor effects.
Up to date, various agents have been used with stem cells as
vehiclestoreducethetumorsizeorextendthesurvivaloftheorganism
[22,23]. All these vehicles and agents showed different success rates. In
the last decade, hMSCs have been proposed as a great tool in different
therapeutic applications. MSCs serve as a powerful cell-based delivery
vehicle for the site-specific release of anticancer drugs due to their
homing abilities, easy acquisition, hypoimmunogenic properties,
fast ex-vivo expansion and feasibility of autologous transplantation
properties [24]. The use of self-derived hMSCs has an advantage over
using other vehicles for delivery since they would have significantly a
lower risk of being rejected as foreign objects by the immune system.
Once these stem cells carrying biological agents are injected into the
patient’s bloodstream, they can migrate to the tumor site and release
the anti-carcinogenic agent.
The use of MSCs transduced with TRAIL showed induction
of apoptosis and a subsequent reduction of tumor cell viability in
colorectal carcinoma, gliomas, lung, breast, squamous and cervical
cancer[25,26].Targeteddeliverywasalsoproventobesuccessfulusing
hMSCs in a xenogenic mouse model. The growth of malignant cells in
lungs of mice was inhibited both in-vitro and in-vivo following local
delivery of MSCs transduced with interferon-β (IFN-β). However,
this inhibition was not achieved during the systematic or non-local
delivery of the cells to the tumor site [27,28]. In the prostate stroma
ABSTRACT
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through
differentiation. Mesenchymal Stem Cells (MSCs) play an important role in tissue homeostasis supporting tissue regeneration. MSCs are
rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great potential in cancer therapy, also the
stem cell exosome and/or microvesicle-mediated tissue regeneration abilities may be used a potential to the therapeutic applications. In
this review, use of hMSCs in stem cell-mediated cancer therapy is discussed.
Keywords: Mesenchymal stem cells; Cancer therapy; Telomere
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International Journal of Stem Cells & Research
to the site of neoplasia of a bladder tumor model and inhibit the
tumor growth as well as prolonged survival of mice [25].
Limiting factors and difficulties of MSC use in cancer
therapy
Difficulties already start with the isolation process, since only 1 in
every 105
cells obtained in isolation is expected to be an MSCs. MSCs
have low grafting efficiency as well as potency. The limited division
potential of hMSCs also restrains their therapeutic applications
especially considering that a high number of cells is required for
therapy in humans. This raises the need for large scale MSC expansion
[22].
Here, the telomere dynamics play an important role in stem cell
function in particular during the expansion of stem cell population.
Telomere homeostasis and telomerase play a critical role in tumor
progression and it is well known that the cancer cells rely on
telomerase for its survival. One of the main functions of telomeres
is to protect the chromosome ends as being detected as DNA double
strand breaks by DNA repair machinery.
Serakinci, et al. [12] established an immortalized human MSCs
(hMSC-telo1) cell line by introducing a retrovirus carrying the
hTERT gene, which codes for the catalytic subunit of telomerase
reverse transcriptase. hTERT, together with hTERC, the telomerase
RNA, function to lengthen the end of DNA strand, namely the
telomeric repeat sequence and allows the stem cell to maintain its
characteristics with an expanded life span This gene manipulation
allowed cells to bypasses the naturally built-in cellular controls which
govern the delicate balance between cell proliferation, senescence,
and carcinogenesis. Although this is very promising in the use
of MSCs for therapeutic applications, manipulation of telomere-
telomerase activity in order to extend the proliferative capacity of
stem cell populations may increase the risk for stem cell susceptibility
to carcinogenesis. The transduced cell line presented variations
indicative of neoplastic development, such as contact inhibition,
anchorage independence and in-vivo tumor formation in Severe
Combined Immunodeficiency (SCID) mice [11]. These can be due
to critically shortened telomeres leading to senescence that can be
considered as a barrier against cancer formation via a telomere-
mediated checkpoint. Dysfunctional telomeres have the ability to
disturb the genomic stability via Break-Fusion-Break cycles causing
excessive genomic instability and aberrations, which might lead to
rapid cell proliferation, loss of contact inhibition, a gradual increase
in telomerase activity [31,32]. These phenotypic and genotypic
alterations were also reported in adipose-derived hMSCs [33] and
bone marrow-derived mouse MSCs [34].
Oneoftheoptionstoresolvetheissueofneoplastictransformation
of hMSCs could be the self-destruction of the vehicle after the drug
delivery. This kind of treatment has been applied in tumor-selective
viruses that mediate oncolytic effects on tumors and destroy targeted
cancer cells. This kind of viruses has been engineered at the telomerase
promoter sequence with tumor-specific transcriptional response
elements. These therapies target the telomerase-positive cells and
combine the genetically engineered vehicle stem cell and suicide
gene therapies [35-37]. Serakinci and colleagues [38] have reported
that hMSC-telo1 cells do not necessarily give rise to spontaneous
transformation. The neoplastic transformation was observed in the
telomerase introduced hMSCs when they were subjected to 2.5 Gy
of gamma irradiation followed by long-term culturing. Thus, the
neoplastic transformation was suggested to occur due to DNA damage
Figure 1: hMSCs mediated gene therapy targeting cancer.
MSCs show the characteristics of self-renew themselves as well as can
differentiate into different cells. hMSCs plays important role in cancer
development and cancer therapy. These cells may undergo neoplastic
transformation with the environmental stimuli, intrinsic and extrinsic
factors. Due to hMSCs shows homing property to injury side, exosomes or
microvesicles, inflammatory or tumour sites to contribute for the tissue or
tumour stroma repair. These properties gives great potential to hMSCs to be
used in cancer therapy as delivery vehicles and to development of stem cell
mediated targeted therapy strategies.
of a castrate resistant mouse model, where MSCs were used to deliver
Frizzled Related Protein-2 (SFRP2) to antagonize the Wnt-mediated
cancer progression, decreased tumor growth, increased apoptosis, and
tumor necrosis have been observed [29]. In mice with both solid and
metastatic tumors, it was shown that intratumoral injection of MSCs
expressing modified interleukin-12 (MSCs/IL-12M) caused strong
tumor-specific T-cell responses and anti-metastatic effects as well as
inhibitory effects of solid tumor growth. These effects were proven to
be stronger than interleukin-12 expressing adenovirus [30]. In 2011,
Serakinci, et al. [10] showed the homing, engrafting and proliferation
abilities of hMSCs in a human xenograft model in an ovarian cancer
cell line transplanted into immune compromised mice [10]. Human
BM-MSCs were shown to secrete interferon-b (IFNb) and diminish
melanoma, breast carcinoma, and lung metastases [25]. Similarly,
MSCs derived from amniotic fluid was capable of transporting IFNb
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International Journal of Stem Cells & Research
caused by irradiation and telomere damage leading to temporary
cell cycle arrest [12,38]. Telomerase may help in the production of
a large number of cells, but it may have an impact on neoplastic
transformation. Therefore these cells require close monitoring before
and after the application and treatment.
In addition to the malignant transformations observed in cells
with manipulated telomere-telomerase activity, unmanipulated BM-
MSCs were also shown to produce a sub-population of cells with high
levels of telomerase activity, chromosomal aneuploidy, translocations
and capacity in the formation of tumors in multiple organs of NOD/
SCID mice [22,39]. Malignant transformations were also reported in
rodent models, in mouse, and in hMSC populations [11,33,22,39].
The underlying molecular mechanism in this spontaneous
transformation was suggested to occur after hMSC by-passing the
senescence by repressing p16 expression, acquisition of telomerase
activity, deletion of the Ink4a/Arf locus and hyperphosphorylation of
Rb [33]. This raised concerns whether hMSCs can lead to spontaneous
malignant transformation when forced to extensive expansion. On
the contrary to these studies, analysis of hMSCs with comparative
genomic hybridization, karyotyping and subtelomeric fluorescence
in situ hybridization showed that there is no evidence of spontaneous
hMSC transformation during long-term culture [40,41]; however,
maintaining a normal karyotype will not eliminate the possibility
of epigenetic changes to occur. Indeed, telomerase-immortalized
hMSCs were shown to accumulate genetic and epigenetic variations
leading to spontaneous transformation [11,42]. Exogenously
administered hMSCs may get engaged to developing tumors, after
being infused systemically in animal models for glioma, colon
carcinoma, gastric cancer, ovarian carcinoma, Kaposi’s sarcoma and
melanoma [43,44]. Although these studies support the possibility of
neoplastic transformation of hMSCs during in-vitro expansion, it is
still controversial and the molecular pathogenesis underlying such
mechanism is not fully established yet.
Moreover, a number of studies investigating the use of MSCs
for graft-versus-host disease showed no signs of tumor formation
[43,45,46]. A recent small size phase 2 clinical study was reported for
the use of MSCs for the treatment of Crohn’s disease that showed
promising results. Although all these results are promising, in order
to establish a definite role of MSC in the prevention of tumorigenesis,
comprehensive information on the regulation of adult stem cell
growth and monitoring the outcome of clinical applications are
necessary.
CONCLUSIONS AND FUTURE DIRECTIONS
Lately, hMSCs have become a great therapeutic target for
many diseases due to their homing abilities once reconstructed
to inflammation or tumor site. MSCs can be acquired from the
patients’ own body and use of these cells lowers the risks of
rejection. In addition to their tumor homing properties, MSCs are
also easily transduced by integrating vectors due to their high levels
of amphotropic receptors and offer long-term gene expression
without alteration of the phenotype. Gene and viral-based therapies
have shown enhancements in cancer treatment and a number of
anticancer genes have been successfully engineered into MSCs, which
then promoted anticancer effects in various carcinoma models.
However, since one of the most apparent characteristics of cancer is
the continued cell growth that is associated with telomerase activity,
there may be an increased risk of cancer development with the use
of genetically modified cells in cancer therapies. Therefore, use of
targeted treatment with self-suicide vehicles may be a better approach
to improve the cancer therapy and reduce the risk of developing a
secondary tumor.
The stem cell exosome/microvesicle-mediated regeneration, cell
migration and homing abilities of the hMSCs had an important role
in the treatment of cancer and other diseases. Several anticancer
genes have been successfully engineered into MSCs. Lentivirus-,
retrovirus-, plasmid- and adenovirus-mediated MSC deliveries
showed promising results in animal studies with prolonged life of
the animals, reduced complications, and/or tumor growth. All these
promising results have drawn the attention to the potential of MSCs
in cell-based therapies. Current literature and discussion indicate that
hMSC use in cancer therapy would benefit from the combination of
the gene therapy with stem cell therapy approach.
It is worth mentioning that use of genetically modified MSCs and
their target specificities need further exploring. Therefore, clinical
studies play a crucial role in determining the potential of MSC usage
in cancer in combination with conventional therapy strategies.
In conclusion, modeling of hMSCs is a promising approach for
cancer therapy. The use of hMSCs with suicidal gene therapies is a
hopeful approach and the combinatory effect of gene therapy with
stem cell therapy may be the strategy forward.
REFERENCES
1. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-
Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from
adult marrow. Nature. 2002; 418: 41-49. https://goo.gl/ZkvAjK
2. Kortesidis A, Zannettino A, Isenmann S, Shi S, Lapidot T, Gronthos S.
Stromal-derived factor-1 promotes the growth, survival, and development
of human bone marrow stromal stem cells. Blood. 2005; 105: 3793-3801.
https://goo.gl/tuYQdr
3. Wynn RF, Hart CA, Corradi-Perini C, O’Neill L, Evans CA, Wraith JE, et al. A
small proportion of mesenchymal stem cells strongly expresses functionally
active CXCR4 receptor capable of promoting migration to bone marrow.
Blood. 2004; 104: 2643-2645. https://goo.gl/X3Zd3L
4. Yang C, Deqiang Lei, Weixiang Ouyang, Jinghua Ren, Huiyu Li, Jingqiong Hu,
et al. Conditioned media from human adipose tissue-derived mesenchymal
stem cells and umbilical cord-derived mesenchymal stem cells efficiently
induced the apoptosis and differentiation in human glioma cell lines in vitro.
BioMed Research International. 2014. https://goo.gl/tdGmn3
5. Calió ML, Marinho DS, Ko GM, Ribeiro RR, Carbonel AF, Oyama LM, et al.
Transplantation of bone marrow mesenchymal stem cells decreases oxidative
stress, apoptosis, and hippocampal damage in brain of a spontaneous
stroke model. Free radical biology & medicine. 2014; 70: 141-154.
https://goo.gl/ne9NeQ
6. Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells.
International Journal of Molecular Sciences. 2014; 15: 4142-4157. https://
goo.gl/Gx1KyE
7. Honoki K, Tsujiuchi T. Senescence bypass in mesenchymal stem cells:
a potential pathogenesis and implications of pro-senescence therapy
in sarcomas. Expert review of anticancer therapy. 2013; 13: 983-996.
https://goo.gl/s4MEyD
8. Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and
tracking. Stem Cells International. 2013. https://goo.gl/TmZdbx
9. D’Souza A, Lacy M, Gertz M, Kumar S, Buadi F, Hayman S, et al. Long-term
outcomes after autologous stem cell transplantation for patients with POEMS
syndrome (osteosclerotic myeloma): A single-center experience. Blood.
2012; 120: 56-62. https://goo.gl/XWDDA9
10. Serakinci N, Christensen R, Fahrioglu U, Sorensen FB, Dagnæs-Hansen
F, Hajek M, et al. Mesenchymal stem cells as therapeutic delivery vehicles
targeting tumor stroma. Cancer biotherapy & radiopharmaceuticals. 2011; 26:
767-773. https://goo.gl/ucgPL5
5. SCIRES Literature - Volume 3 Issue 1 - www.scireslit.com Page - 0011
International Journal of Stem Cells & Research
11. Serakinci N, Guldberg P, Burns JS, Abdallah B, Schrødder H, Jensen T, et al.
Adult human mesenchymal stem cell as a target for neoplastic transformation.
Oncogene. 2004; 23: 5095-5098. https://goo.gl/w7CLnM
12. Serakinci N, Christensen R, Graakjaer J, Cairney CJ, Keith WN, Alsner J, et
al. Ectopically hTERT expressing adult human mesenchymal stem cells are
less radiosensitive than their telomerase negative counterpart. Experimental
Cell Research. 2007; 313: 1056-1067. https://goo.gl/XMrznI
13. Bentzon JF, Stenderup K, Hansen FD, Schroder HD, Abdallah BM, Jensen
TG, et al. Tissue distribution and engraftment of human mesenchymal
stem cells immortalized by human telomerase reverse transcriptase gene.
Biochemical and Biophysical Research Communications. 2005; 330: 633-
640. https://goo.gl/bsNFpl
14. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of
mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose
tissue. Stem cells. 2006; 24: 1294-1301. https://goo.gl/mFUqZY
15. Mueller SM, Glowacki J. Age-related decline in the osteogenic potential of
human bone marrow cells cultured in three-dimensional collagen sponges.
Journal of cellular biochemistry. 2001; 82: 583-590. https://goo.gl/6w9bl3
16. Vellasamy S, Sandrasaigaran P, Vidyadaran S, George E, Ramasamy
R. Isolation and characterisation of mesenchymal stem cells derived
from human placenta tissue. World journal of stem cells. 2012; 4: 53-61.
https://goo.gl/UaFfL9
17. Batsali AK, Kastrinaki MC, Papadaki HA, Pontikoglou C. Mesenchymal stem
cells derived from Wharton’s Jelly of the umbilical cord: biological properties
and emerging clinical applications. Current stem cell research & therapy.
2013; 8: 144-155. https://goo.gl/Ui03GQ
18. Rubinstein P, Dobrila L, Rosenfield RE, Adamson JW, Migliaccio G,
Migliaccio AR, et al. Processing and cryopreservation of placental/umbilical
cord blood for unrelated bone marrow reconstitution. Proceedings of the
National Academy of Sciences of the United States of America. 1995; 92:
10119-10122. https://goo.gl/KJZTcQ
19. Wyrsch A, Dalle Carbonare V, Jansen W, Chklovskaia E, Nissen C,
Surbek D, et al. Umbilical cord blood from preterm human fetuses is rich
in committed and primitive hematopoietic progenitors with high proliferative
and self-renewal capacity. Experimental Hematology. 1999; 27: 1338-1345.
https://goo.gl/TNaucL
20. Goodwin H, Bicknese AR, Chien SN, Bogucki BD, Quinn CO, Wall DA.
Multilineage differentiation activity by cells isolated from umbilical cord blood:
Expression of bone, fat, and neural markers. Biology of Blood and Marrow
Transplantation. 2001; 7: 581-588. https://goo.gl/49mmUI
21. Chang Y, Tseng CP, Hsu LF, Hsieh TB, Hwang SM. Characterization of two
populations of mesenchymal progenitor cells in umbilical cord blood. Cell
Biology International. 2006; 30: 495-499. https://goo.gl/OfIjsV
22. Momin EN, Mohyeldin A, Zaidi HA, Vela G, Quiñones-Hinojosa A.
Mesenchymal stem cells: new approaches for the treatment of neurological
diseases. Current stem cell research & therapy. 2010; 5: 326-344.
https://goo.gl/gxqcmk
23. Aboody KS, Najbauer J, Danks MK. Stem and progenitor cell-mediated
tumor selective gene therapy. Gene therapy. 2008; 15: 739-752.
https://goo.gl/tt5CWO
24. Gao Z, Zhang L, Hu J, Sun Y. Mesenchymal stem cells: A potential
targeted-delivery vehicle for anti-cancer drug, loaded nanoparticles.
Nanomedicine: Nanotechnology, Biology, and Medicine. 2013; 9: 174-184.
https://goo.gl/Ty3YTT
25. Shah K. Encapsulated stem cells for cancer therapy. Biomatter. 2013; 3:
e24278. https://goo.gl/dxtXVZ
26. Menon LG, Kelly K, Yang HW, Kim SK, Black PM, Carroll RS. Human bone
marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular
delivery vehicle for human glioma therapy. Stem Cells. 2009; 27: 2320-2330.
https://goo.gl/W0ChFf
27. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M.
Bone marrow-derived mesenchymal stem cells as vehicles for interferon-
beta delivery into tumors. Cancer research. 2002; 62: 3603-3608.
https://goo.gl/ZwUD3t
28. Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M,
Bekele BN, et al. Mesenchymal stem cells: Potential precursors for tumor
stroma and targeted-delivery vehicles for anticancer agents. Journal of the
National Cancer Institute. 2004; 96: 1593-1603. https://goo.gl/fNwbAe
29. Placencio VR, Li X, Sherrill TP, Fritz G, Bhowmick NA. Bone marrow derived
mesenchymal stem cells incorporate into the prostate during regrowth. PLoS
One. 2010; 5: e12920. https://goo.gl/gu05ss
30. Seo SH, Kim KS, Park SH, Suh YS, Kim SJ, Jeun SS, et al. The effects
of mesenchymal stem cells injected via different routes on modified
IL-12-mediated antitumor activity. Gene therapy. 2011; 18: 488-495.
https://goo.gl/hSBzYb
31. Serakinci N, Graakjaer J, Kolvraa S. Telomere stability and telomerase in
mesenchymal stem cells. Biochimie. 2008; 90: 33-40. https://goo.gl/5r2Sen
32. Furlani D, Ugurlucan M, Ong L, Bieback K, Pittermann E, Westien I, et
al. Is the intravascular administration of mesenchymal stem cells safe?
Mesenchymal stem cells and intravital microscopy. Microvascular Research.
2009; 77: 370-376. https://goo.gl/ZN6yyH
33. Rubio D, Garcia S, De la Cueva T, Paz MF, Lloyd AC, Bernad A, et al. Human
mesenchymal stem cell transformation is associated with a mesenchymal-
epithelial transition. Experimental Cell Research. 2008; 314: 691-698.
https://goo.gl/R606S2
34. Miura Y, Gao Z, Miura M, Seo BM, Sonoyama W, Chen W, et al. Mesenchymal
stem cell-organized bone marrow elements: an alternative hematopoietic
progenitor resource. Stem cells. 2006; 24: 2428-2436. https://goo.gl/Ss3eJl
35. Abdul-Ghani R, Ohana P, Matouk I, Ayesh S, Ayesh B, Laster M, et al. Use
of transcriptional regulatory sequences of telomerase (hTER and hTERT)
for selective killing of cancer cells. Molecular therapy : the journal of the
American Society of Gene Therapy. 2000; 2: 539-544. https://goo.gl/ygFxn4
36. Komata T, Koga S, Hirohata S, Takakura M, Germano IM, Inoue M, et al. A
novel treatment of human malignant gliomas in vitro and in vivo: FADD gene
transfer under the control of the human telomerase reverse transcriptase
gene promoter. Int J Oncol. 2001; 19: 1015-1020. https://goo.gl/tQ0nec
37. Plumb JA, Bilsland A, Kakani R, Zhao J, Glasspool RM, Knox RJ, et al.
Telomerase-specific suicide gene therapy vectors expressing bacterial
nitroreductase sensitize human cancer cells to the pro-drug CB1954.
Oncogene. 2001; 20: 7797-7803. https://goo.gl/meuR66
38. Christensen R, Alsner J, Brandt Sorensen F, Dagnaes-Hansen F, Kolvraa S,
Serakinci N. Transformation of human mesenchymal stem cells in radiation
carcinogenesis: long-term effect of ionizing radiation. Regenerative medicine
2008; 3: 849-861. https://goo.gl/QwnnQu
39. Wang Y, Huso DL, Harrington J, Kellner J, Jeong DK, Turney J, et al.
Outgrowth of a transformed cell population derived from normal human
BM mesenchymal stem cell culture. Cytotherapy. 2005; 7: 509-519.
https://goo.gl/tBdCAh
40. Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A,
et al. Human bone marrow-derived mesenchymal stem cells do not undergo
transformation after long-term in vitro culture and do not exhibit telomere
maintenance mechanisms. Cancer Research. 2007; 67: 9142-9149.
https://goo.gl/TxejGk
41. Meza-Zepeda LA, Noer A, Dahl JA, Micci F, Myklebost O, Collas P. High-
resolution analysis of genetic stability of human adipose tissue stem cells
cultured to senescence. Journal of cellular and molecular medicine. 2008; 12:
553-563. https://goo.gl/44l3hZ
42. Burns JS, Abdallah BM, Guldberg P, Rygaard J, Schrøder HD, Kassem
M. Tumorigenic heterogeneity in cancer stem cells evolved from long-term
cultures of telomerase-immortalized human mesenchymal stem cells. Cancer
Research. 2005; 65: 3126-3135. https://goo.gl/Cnbd8z
43. Correa P, Houghton J. Carcinogenesis of Helicobacter pylori.
Gastroenterology. 2007; 133: 659-672. https://goo.gl/Fyx8xK
44. Lazennec G, Jorgensen C. Concise review: adult multipotent stromal
cells and cancer: risk or benefit? Stem cells. 2008; 26: 1387-1394.
https://goo.gl/lF7NK7
45. Barkholt L, Flory E, Jekerle V, Lucas-Samuel S, Ahnert P, Bisset L, et al. Risk
of tumorigenicity in mesenchymal stromal cell-based therapies - Bridging
scientific observations and regulatory viewpoints. Cytotherapy. 2013; 15:
753–759. https://goo.gl/lXOjXv
46. Resnick IB, Barkats C, Shapira MY, Stepensky P, Bloom AI, Shimoni A, et
al. Treatment of severe steroid resistant acute GVHD with mesenchymal
stromal cells (MSC). American journal of blood research. 2013; 3: 225-238.
https://goo.gl/svjCF0