Stem cells offer potential treatments for many conditions like diabetes, Parkinson's disease and heart disease. Research is focused on better understanding stem cell types like embryonic, adult and induced pluripotent stem cells. Challenges include identifying growth factors, avoiding immune rejection, and safety issues like preventing malignancy. Recent studies show stem cells improving conditions in animal models of diseases like hemophilia and spinal cord injury. Clinical trials are beginning to test stem cell therapies for conditions like ALS. Overall stem cells represent an exciting area of research towards regenerative medicine.
Due to everyday changing lifestyle, many couples suffers from infertility issues and as a solution to this stem cells therapy comes up in the front line.Know more in detail about infertility and application of stem cells.
interest in stem cells is raising in different field of medicine. The question is : is it successful in Gynecology or it is still too early to say that. The present talk may help to explore this .
Due to everyday changing lifestyle, many couples suffers from infertility issues and as a solution to this stem cells therapy comes up in the front line.Know more in detail about infertility and application of stem cells.
interest in stem cells is raising in different field of medicine. The question is : is it successful in Gynecology or it is still too early to say that. The present talk may help to explore this .
Public lecture - Stem Cell and Male InfertilitySandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Public Lecture - Stem Cell and Male Infertility
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
It was while performing SUZI that a single spermatozoon accidentally penetrated into the oolemma and provided the hint that a direct sperm injection would be more efficient.
1st successful birth by ICSI took place on Jan 14, 1992.
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
ICSI as it is presently performed is far from an ideal solution because the selection of sperm is based on the judgement of an embryologist, who is looking for the most normal appearing sperm available.
EMBRYO QUALITY ASSESSMENT, WHICH TO SELECT? Rahul Sen
Traditional embryo evaluation systems are simple, non-invasive, cost-effective & mainstay in majority of IVF laboratories. Embryo selection based on combinations of morphology scores at different stages of embryonic development with time may be more effective
Stem cells are the promising cells that are capable to differentiate into any deserved cell type. By using stem cells we can generate tissues and even organs that can be used in multiple disciplines as drug testing, as a source used for organ transplantation...etc.
Blood production agency. all types of blood cellls are produced in it. to understand it is the need of this era. it also will help in the physiology of blood making mechanism.
Public lecture - Stem Cell and Male InfertilitySandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Public Lecture - Stem Cell and Male Infertility
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
It was while performing SUZI that a single spermatozoon accidentally penetrated into the oolemma and provided the hint that a direct sperm injection would be more efficient.
1st successful birth by ICSI took place on Jan 14, 1992.
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
Sperm DNA Fragmentation (Oxidative stress, DNA damage and apoptosis, Test, Techniques, Relation to other semen parameters, Relationship to leucocytes, Relation to ICSI outcomes, Clinical applications, significance and limitations)
ICSI as it is presently performed is far from an ideal solution because the selection of sperm is based on the judgement of an embryologist, who is looking for the most normal appearing sperm available.
EMBRYO QUALITY ASSESSMENT, WHICH TO SELECT? Rahul Sen
Traditional embryo evaluation systems are simple, non-invasive, cost-effective & mainstay in majority of IVF laboratories. Embryo selection based on combinations of morphology scores at different stages of embryonic development with time may be more effective
Stem cells are the promising cells that are capable to differentiate into any deserved cell type. By using stem cells we can generate tissues and even organs that can be used in multiple disciplines as drug testing, as a source used for organ transplantation...etc.
Blood production agency. all types of blood cellls are produced in it. to understand it is the need of this era. it also will help in the physiology of blood making mechanism.
The ISSCR is an independent, nonprofit organization providin.docxoreo10
The ISSCR is an independent, nonprofit
organization providing a global forum for
stem cell research and regenerative medicine.
Stem Cell
Facts
What are stem cells?
Stem cells are the foundation cells for every organ and
tissue in our bodies. The highly specialized cells that make
up these tissues originally came from an initial pool of stem
cells formed shortly after fertilization. Throughout our lives,
we continue to rely on stem cells to replace injured tissues
and cells that are lost every day, such as those in our skin,
hair, blood and the lining of our gut. Stem cells have two
key properties: 1) the ability to self-renew, dividing in a
way that makes copies of themselves, and 2) the ability to
differentiate, giving rise to the mature types of cells that
make up our organs and tissues.
Tissue-specific stem cells
Tissue-specific stem cells, which are sometimes referred to
as “adult” or “somatic” stem cells, are already somewhat
specialized and can produce some or all of the mature
cell types found within the particular tissue or organ in
which they reside. Because of their ability to generate
multiple, organ-specific, cell types, they are described as
“multipotent.” For example, stem cells found within the
adult brain are capable of making neurons and two types of
glial cells, astrocytes and oligodendrocytes.
Tissue-specific stem cells have been found in several organs
that need to continuously replenish themselves, such as the
blood, skin and gut and have even been found in other, less
regenerative, organs such as the brain. These types of stem
cells represent a very small population and are often buried
deep within a given tissue, making them difficult to identify,
isolate and grow in a laboratory setting.
Neuron – Dr. Gerry Shaw, EnCor Biotechnology Inc.
Astrocyte – Abcam Inc.
Oligodendrocyte – Dhaunchak and Nave (2007).
Proc Natl Acad Sci USA 104:17813-8
www.isscr.org
Embryonic stem cells
Embryonic stem cells have been derived from a variety
of species, including humans, and are described as
“pluripotent,” meaning that they can generate all the
different types of cells in the body. Embryonic stem cells
can be obtained from the blastocyst, a very early stage
of development that consists of a mostly hollow ball of
approximately 150-200 cells and is barely visible to the
naked eye. At this stage, there are no organs, not even
blood, just an “inner cell mass” from which embryonic stem
cells can be obtained. Human embryonic stem cells are
derived primarily from blastocysts that were created by
in vitro fertilization (IVF) for assisted reproduction but
were no longer needed.
The fertilized egg and the cells that immediately arise in the
first few divisions are “totipotent.” This means that, under
the right conditions, they can generate a viable embryo
(including support tissues such as the placenta). Within a
matter of days, however, these cells transition to become
pluripote ...
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- 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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
For Better Surat #ℂall #Girl Service ❤85270-49040❤ Surat #ℂall #Girls
Stem cells and infertility by Dr. Gayathiri
1. STEM CELLS AND INFERTILITY
Dr. Gayathiri Ganesan Ram
MS(O.G), Fellow in Reproductive Medicine and
Andrology.
Consultant Reproductive Medicine Specialist
ARC Fertility Hospitals
2. ‘68
‘78
‘81
‘94
‘95
‘96
‘98
‘01
‘05
‘06
‘07
Edwards and Bavister fertilize
first human egg
Mouse embryonic stem cells
derived
Non-human primate ES cells
derived
Thomson et al derive and
culture first hES cells
Woo-suk Hwang fakes human
stem cell cloning
Yamanaka et al derive human
iPS cells
First IVF baby Louise Brown
is born
First donated blastocysts
for research
Dolly, the cloned sheep, is
born at the Roslin Institute
Mouse embryonic stem cells
derived by SCNT
Yamanaka et al derive
mouse iPS cells
A Walk Through the History…
3. Human embryonic stem cell: Also known as a
human pluripotent stem cell, one of the "cells
that are self-replicating, are derived from human
embryos or human fetal tissue, and are known to
develop into cells and tissues of the three
primary germ layers."
(From the National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells.)
Definition
4. Human Embryonic Stem Cells.
• Definition: Stem cells are
clonogenic,undifferentiated, self replicating,
progenitor cells, capable of self regeneration
and also of multilineage differentiation and
generation of several other tissues and organs
in the body
6. Totipotent Stem Cells.
• Natural identical twinning is due to division of
an early embryo into two embryos.
• One form of cloning would be by dividing an
early embryo into two or more embryos.
7. Toti Potent Stem Cells
• The embryonic cells
in the early stages are
toti potent. Eg: two
celled embryo,four
celled embryo.
8. Pluripotent Stem Cells
• Pluri potent cells are capable of producing all
the cells, tissues and organs in the body- but
not an embryo.
• Cells obtained from the blastocyst -from the
inner cell mass are-pluri potent.
9. Pluri Potent Stem Cells
• The cells from the
inner cell mass are
pluri potent. They are
capable of producing
any organ or tissue in
the body-but not the
placenta.
10. Stem Cell Cultivation
• The slide briefly
describes embryonal
stem cell cultivation.
• University of
Wisconsin was the
first one to cultivate
human embryonic
stem cells.
12. Multi Potent Stem Cells
• Adult stem cells, cord blood stem cells,and
cells obtained from late stage embryos are
multi potent.
• Multi potent stem cells are capable of
generation of several tissues, but not all
tissues.
13. Uni potent Stem Cells
• Oxymoron?
• The stem cells found in many organs like
liver,bone marrow,testes serve as reserve cells
for regeneration of appropriate tissue.
• Under proper in vitro/in vivo conditions these
cells can be coaxed to become other tissues of
the body.
14. Embryonic Stem Cells
• These cells are obtained usually from the
inner cell mass of a blastocyst- day 6/7
embryo.
• These embryos are usually spare embryos,
research embryos or orphaned
embryos,obtained from an infertility clinic.
16. Adult Stem Cells
• These cells are generally obtained from bone
marrow.They may also be obtained from
peripheral blood.
• Stem cells are probably present in most of the
tissues and organs in the body.
• It is difficult to identify, isolate culture and
grow adult stem cells.
17. Adult Stem Cells
• Identifying and isolating adult stem cells from
many tissue would be worse than the
proverbial search for ‘needle in a haystack.’
• If this becomes possible, this would avoid
many of the legal, ethical and moral problems
associated with the use of Embryonal stem
cells.
19. Cord Blood Stem Cells
• Cord blood is a good source of stem cells.
• It may be a good idea to store cord blood
routinely at all deliveries for autologous stem
cell transplant or HLA compatible stem cell
transplant- where the older sibling/ other
family members are afflicted with
haematological abnormalities/ malignancy.
20. Indications for Stem Cell Therapy.
• Stem cell therapy can be used in many
degenerative diseases.
• Stem cells can be used in the regeneration of
many diseased organs.
• Stem cells can be used in the correction of
many metabolic and haematologic disorders.
21. Indications for Stem Cell Therapy.
• Current:
• 1)diabetes mellitus- insulin dependent.
• 2)Parkinson’s disease.
• 3)heart disease- both ischaemic and
degenerative.
23. Indications for Stem Cell
Therapy.
• Virtually any diseased organ or tissue can be
replaced with stem cell therapy, obviating the
need for transplants.
• Future research holds very great promise for
correcting many diseases.
• A new specialty is emerging “regenerative
medicine’ thanks to the advent of stem cell
therapy.
24. Mode of Administration of Stem Cells.
• 1)direct injection into the organ.
• 2)systemic administration and the stem cells
colonize the organ/tissue.
• 3)direct surgical placement of stem cells.
26. • Allows for avoidance of immune problems
• Provides patient-specific disease models for
research
• Could lead to reproductive cloning
• Needs the donation of eggs
SCNT
27. Stem cells and the reproductive tract
• Stem cells and the endometrium
• In humans, regeneration of the endometrium
occurs monthly during reproductive life and
beyond under appropriate ovarian steroid
priming.
• Cyclic replenishment of the cellular
compartments of the endometrial functionality
by adult stem cells (ASC) is essential for the
preparation of this organ for its main function,
i.e. allowing implantation and pregnancy to
proceed
28. • ASC present a MSC phenotype (Chan et al.,
2004; Schwab and Gargett, 2007; Schwab et
al., 2008; Cervello et al., 2010)
• They functionally contribute to human
endometrial regeneration in vitro and in vivo
(Cervello et al., 2010, 2011; Matsuda and Shi,
2010).
29. • Bone marrow-derived stem cells (BMDSCs) have been
shown to contribute as an exogenous source to tissue
repair and regeneration of different organs and tissues
(Pittenger et al., 1999).
• In the human, BMDSCs are also a source of non-
hematopoietic cells in the different endometrial cellular
compartments (stroma, glandular epithelium, and luminal
epithelium).
• They contribute mainly to the formation of endometrial
stromal compartment cells and to a much lesser extent to
the glandular and luminal epithelium (Du and Taylor, 2007;
Mints et al.,2008; Ikoma et al., 2009; Cervello et al., 2012).
30. • It has been recently proposed that BMDSC
infusion might improve endometrial regeneration
in a murine model of AS (Alawadhi et al., 2014;
Jing et al., 2014; Kilic et al.,2014; Zhao et al.,
2015).
• However, peripheral blood stem cell
transplant(PBSCT) did not result in engraftment
of donor stemcells in the recipient uterus in a
macaque model, or human (Wolff et al., 2013).
31. SPERMATOZOA
• Obtaining PGCs (primodial germ cells) from pluripotent
cells is the first step in the differentiation toward post-
meiotic spermatozoa. However, further differentiation
has proven challenging in vitro.
• The strategies employed to favor it include
supplementing the differentiation medium with the
growth factors bone morphogenetic protein (BMP)-4, -
7, -8b (Geijsen et al.,2004; Tilgner et al., 2008), N2B27,
activin, Fibroblast growth factor 2 (FGF2) (Hayashi et
al., 2011), retinoid acid (Nayernia et al., 2006;Eguizabal
et al., 2009, 2011; Cai et al., 2013; Peng et al.,
2013),R115866 (Eguizabal et al., 2011), and hormones
such as Insulin andTestosterone (Easley et al., 2012).
32. STEM CELLS AND VAGINAL
RECONSTRUCTION
• The use of stem cells for vaginal recovery has
been poorly investigated so far, but most work
has been carried out with muscle-derived stem
cells (MDSC).
• Recently, muscle has been identified as an
alternative source of adult stem cells, different
from satellite cells, possessing the capacity to
differentiate into different cell lineages.
• MDSCs appear as promising candidates for the
treatment of muscular, cardiac and urological
disorders.
33. STEM CELLS AND ERECTILE
DYSFUNCTION
• Penile erection is a neurovascular response
involving an increase in arterial inflow, relaxation
of corpora smooth muscles, and a reduction
invenous outflow.
• Erectile dysfunction can be caused by conditions
such as diabetes, neuropathies, cavernous nerve
injuries, neurotransmitterimbalances, vascular
diseases, inflammation diseases (Peyronie
• disease) or surgery.
34. • The results obtained indicated that the stem cell
injections brought benefits in terms of restored
erectile function and penile physiology (Zhang et
al., 2012); interestingly, the improvement in
erectile function seems to be due to the
paracrine factors secreted by the injected cells
(cytoprotective, anti-fibrotic and anti-apoptotic
molecules),rather than direct
grafting/differentiation (Albersen et al., 2010).
• No informationis available on the duration of the
beneficial effects.
35. • The only preclinical study involving patients was
carried out with intracavernosal injections of
umbilical cord blood stem cells in seven patients
with diabetic-erectile dysfunction: patients
reported an improvement in penile erection and
an increase in penile rigidity, especially when in
combination with PDE5 inhibitors; the duration of
the effect was variable but after a few months all
patients experienced a regression
• (Bahk et al.,2010).
36. Current Research
• 1) current research is aimed at identifying,
isolating, culturing and growing embryonal
stem cells and adult stem cells.
• 2) identifying organizers/ growth factors which
direct stem cells to grow into different tissue
and organs.
37. Current Research
• 3)modifying adult multi potent stem cells to pluri
potent stem cells.
• 4) engineering stem cells to avoid expression of HLA
antigen which often lead to immune rejection.
• 5) optimizing the conditions for inducing
pluripotyency by expressing transgenes in somatic
cells
• 6) carefully characterizing the genetic and epigenetic
abnormalities of current stem cells to avoid
malignancy in the patient
38. 2002
◦ Stem Cells "Cure" Diabetes in Mouse – Stanford
◦ Stem Cells Improve Motor Function in Rat Model of
Parkinson's Disease - NIH
2003
◦ Mouse Embryonic Stem Cells Develop Into Sperm – Japan
◦ Human Embryonic Germ Cells Restore Movement to
Paralyzed Rats – Johns Hopkins
2004
◦ Heart Muscle Cells Produced from Human Embryonic Stem
Cells Can Replace Biological Pacemaker – Israel
◦ Mouse Sperm Generated from Stem Cells Able to Fertilize
Mouse Egg - Harvard
Research Highlights of the Field
39. 2005
◦ Embryonic Stem Cells Cure Mouse Model of Hemophilia – UNC
Chapel Hill
◦ Alternative Method for Deriving Stem Cells Proven in Mice – MIT
2006
◦ Scientists Generate Human Embryonic Stem Cell Lines from
Single Cells – Advance Cell Technology
◦ Scientists Reprogram Adult Mouse Skin Cells by Adding Defined
Factors – Japan
2007
◦ Reprogrammed Mouse Skin Cells Cure Mouse Sickle Cell Anemia
– MIT
◦ Human Skin Cells Reprogrammed – Japan
Research Highlights of the Field
40. • 2008
– Scientists Generate Stem Cell Line from Patient
with ALS Disease – Harvard
– Adult Stem Cell Lines Created for 10 Additional
Human Diseases – Harvard
• 2009
– Geron Receives FDA Clearance to Begin World's
First Human Clinical Trial of Embryonic Stem Cell-
Based Therapy
Research Highlights of the Field
Editor's Notes
Stem Cells "Cure" Diabetes in MouseUsing funds from sources other than NIH, scientists at Stanford University recently reported that they could use mouse embryonic stem cells to "cure" a mouse model of diabetes. The mouse stem cells were treated with growth inhibitors and displayed characteristics of pancreatic beta cells, including release of insulin in response to glucose in the culture medium, prior to their implantation in the diabetic mouse. Their results suggest that embryonic stem cells could serve as a source of insulin-producing replacement tissue and provide hope that this technique, adapted to human embryonic stem cells, may lead to a cure for human diabetes patients. (Proceedings of the National Academy of Sciences of the USA 99:16105–16110, 2002, laboratory of S.K. Kim)
Stem Cells Improve Motor Function in Rat Model of Parkinson's Disease
Using mouse embryonic stem cells, NIH intramural researchers from the National Institute on Neurological Disorders and Stroke (NINDS) were able to derive neurons that secreted dopamine and demonstrated anatomical, behavioral, and physiological characteristics of the neurons lost in Parkinson's disease. When grafted into rat models of Parkinson's disease, the cells were able to improve motor function. This work in an animal model demonstrates the potential of embryonic stem cells for treating human diseases. (Nature 418:50–56, 2002, laboratory of R. McKay)
Human Embryonic Germ Cells Restore Movement to Paralyzed RatsUsing pluripotent cells derived from human embryonic germ cells, scientists not funded by the NIH have been able to partially restore paralyzed rats' ability to move. The rats serve as an animal model of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Transplanted pluripotent cells migrate into the spinal cord of paralyzed rats and prevent existing host neurons from dying. The cells seem to restore mobility by secreting factors that promote the regrowth of connections between ingrowing nerves and motor neurons. This work provides hope that scientists may one day be able to use pluripotent cells to restore movement to patients suffering from Lou Gehrig's disease. (The Journal of Neuroscience 23:5131–5140, 2003, laboratories of J.D. Gearhart and J.D. Rothstein)
Mouse Embryonic Stem Cells Develop Into SpermJapanese-funded researchers were able to coax male mouse embryonic stem cells into becoming germ cells, which have the potential in males to produce sperm or in females to produce egg cells. When transplanted into mouse testis, the male germ cells gave rise to mature sperm. If these results can be repeated with human embryonic stem cells, scientists would have a valuable new source of cells to study how human germ cells and sperm cells are specified. A better understanding of how sperm are generated may lead to new treatments for male infertility. (Proceedings of the National Academy of Sciences of the USA 100:11457–11462, 2003, laboratory of T. Noce)
Heart Muscle Cells Produced from Human Embryonic Stem Cells Can Replace Biological PacemakerA heart attack occurs when the supply of blood and oxygen to an area of heart muscle is blocked. Often, this blockage leads to arrhythmias (irregular heartbeat or rhythm) that cause a severe decrease in the pumping function of the heart and may bring about sudden death. If the blockage is not treated within a few hours, the affected heart muscle will die and be replaced by scar tissue. Transplantation of heart muscle cells is one possible therapy, but supplies of such cells are very limited. Scientists supported by the Israeli government and private funds produced heart muscle cells from human embryonic stem cells (hESCs) listed on the NIH Stem Cell Registry. The hESC-derived heart muscle cells beat in synchrony with newborn rat heart muscle cells after being cultured together for 24 hours. Transplanted hESC-derived heart muscle cells were also able to restore heart rhythm in 11 out of 13 pigs whose biological pacemaker had been damaged. If this work can be repeated in human beings, scientists may be able to use these cells to replace human heart pacemakers rather than the current implanted electronic devices. (Nature Biotechnology 22:1282–1289, laboratory of L. Gepstein)
Mouse Sperm Generated from Stem Cells Able to Fertilize Mouse EggEarlier in 2003, Japanese scientists were able to generate mouse sperm using mouse embryonic stem cells (see Mouse Embryonic Stem Cells Develop into Sperm). Now, a group of NIH-funded scientists in Massachusetts has generated sperm from mouse embryonic stem cells and demonstrated that they can fertilize a mouse egg. Because the sperm cells did not have a tail, the scientists had to inject them into mouse eggs to accomplish fertilization. Scientists may now be able to generate sperm in the laboratory to study how they regulate gene expression and other important events during development. (Nature 427:148–154, laboratory of G.Q. Daley)
Embryonic Stem Cells Cure Mouse Model of HemophiliaHemophilia is a rare inherited disorder in which the blood does not clot normally. The disease is caused when the liver does not produce any (or insufficient amounts of) blood clotting factors. Individuals with hemophilia can be treated with infusions of blood clotting factors, but these only help for a short time. Scientists are searching for ways to permanently restore these individuals' blood-clotting ability. NIH-supported scientists used stem cells to cure mice suffering from a disorder similar to human Hemophilia B. The scientists incubated mouse embryonic stem cells for 7 days with a growth factor called FGF, for Fibroblast Growth Factor. After this treatment, the cells' protein-producing machinery stopped making templates for embryonic proteins and began making templates for proteins of early digestive system cells. When injected into the livers of "hemophilic" mice, the cells survived and made the missing blood-clotting factors. If these results can be repeated in human beings, doctors may one day be able to use human embryonic stem cells (hESCs) to restore blood clotting abilities to individuals with hemophilia. (Proceedings of the National Academy of Sciences of the USA 102:2958–2963, laboratories of O. Smithies and J. Frelinger)
Alternative Method for Deriving Stem Cells Proven in MiceA technique called "Altered Nuclear Transfer" (ANT) proposes to create patient-specific stem cells without destroying an embryo. In traditional nuclear transfer, patient-specific stem cells are created by removing the nucleus from a donated human egg and replacing it with the nucleus (usually from a skin cell) of a patient. Scientists stimulate the egg to divide, and destroy the embryo after 5 days to collect what will become human embryonic stem cells. ANT proposes that scientists turn off a gene needed for implantation in the uterus (Cdx2) in the patient cell nucleus before it is transferred into the donor egg. The proponents of ANT attempt to address concerns about embryo destruction by suggesting that because the entity created is unable to implant in the uterus, it is not a true embryo. NIH-supported scientists recently reported proof of principle tests that ANT works in mice. Mouse ANT entities whose Cdx2 gene is switched off are unable to implant in the uterus and do not survive to birth. However, scientists used ANT to create viable stem cell lines capable of producing almost all cell types. The authors point out that this technique must still be tested with monkey and human embryos, and the manipulation needed to control Cdx2 expression introduces another logistical hurdle that may complicate ANT's use to derive embryonic stem cells. (Nature 439(7073):212–5, laboratory of R. Jaenisch)
Scientists Generate Human Embryonic Stem Cell Lines from Single CellsIn 2005, privately funded scientists demonstrated that it was possible to remove a single cell from a pre-implantation mouse embryo and generate a mouse embryonic stem cell line (see Fertility Clinic Technique Modified to Derive Stem Cells). Now, these scientists report that they have successfully established human embryonic stem cell lines from single cells taken from pre-implantation human embryos. The human stem cells created using this technique behaved like pluripotent stem cells, including making proteins critical for "stemness" and being able to produce cells from all three germ layers. Proponents of this technique suggest that since it requires only one cell from the embryo, the remaining cells may yet be implanted in the womb and develop into a human being. Thus scientists could potentially derive human embryonic stem cells without having to destroy an embryo. However, ethical considerations make it uncertain whether scientists will ever test if the cells remaining after removal of a single cell can develop into a human being, at least in embryos that are not at risk for carrying a genetic disorder. (Nature advance online publication, laboratory of R. Lanza)
Scientists Reprogram Adult Mouse Skin Cells by Adding Defined FactorsScientists have previously reported being able to "reprogram," or turn back the clock on adult cells, to make them behave as embryonic stem cells (see Human Embryonic Stem Cells Can Reprogram Adult Human Cells). However, the previous method fused a human embryonic stem cell with an adult human cell, producing a hybrid cell with four copies of the cellular DNA (tetraploid) rather than the normal two copies (diploid). Recently, scientists funded by the Japanese government reported that they could reprogram adult mouse skin cells by engineering the cells to express four defined factors: Oct3/4, Sox2, c-Myc, and Klf4, and growing the cells using embryonic stem cell culture conditions. The four factors are known to be important for maintaining the "stemness" of embryonic stem cells. The scientists called the reprogrammed adult cells "iPS" for "induced pluripotent stem" cells. iPS demonstrated important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all 3 germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Scientists will now try to determine if human adult cells can also be reprogrammed using this method. (Cell 126:1–14, laboratory of S. Yamanaka)
Reprogrammed Mouse Skin Cells Cure Mouse Sickle Cell AnemiaIndividuals with sickle cell anemia inherit a defective hemoglobin gene that causes their red blood cells (RBCs) to assume a sickle shape. The sickled RBCs clump together and block blood flow, causing pain and organ damage. NIH-funded scientists used a published method (see Human Skin Cells Reprogrammed) to reprogram mouse skin cells derived from a mouse carrying the defective hemoglobin gene, producing induced pluripotent stem cells (iPS cells). They then used homologous recombination to repair the defective hemoglobin gene and directed the iPS cells to become blood-forming (hematopoietic) stem cells. Hematopoietic stem cells are found in bone marrow and produce all the blood cells in the body. Finally, the scientists transplanted the repaired hematopoietic stem cells into the bone marrow of sickle cell mice whose own marrow was destroyed in order to eliminate the defective hematopoietic cells. The transplanted cells were able to regenerate the mice's blood systems, including production of normal rather than sickled red blood cells. This research advance demonstrates that reprogrammed adult mouse cells (iPS cells) are capable of producing cells that can treat disease in mice. However, the methods used in this study include use of a cancer-promoting gene and inactivated viruses, and are not likely to be used to treat humans. If scientists can develop safer methods to reprogram adult cells, iPS cells could one day generate cells and tissues to treat human diseases. Science 318:1920–23, laboratory of R. Jaenisch. 2007 Dec 6.
Human Skin Cells ReprogrammedIn 2006, Japanese scientists were able to reprogram adult mouse skin cells to behave like mouse embryonic stem cells, although the reprogrammed cells could not produce eggs or sperm (gametes). The scientists named the cells iPS cells, for induced pluripotent stem cells. In 2007, the Japanese researchers successfully generated gametes from iPS cells, and their results were verified and extended by another independent laboratory. Now, simultaneous publications from the Japanese scientists and a team of NIH-supported scientists report that they have each succeeded at reprogramming adult human skin cells to behave like human embryonic stem cells (hESCs). The Japanese team forced adult skin cells to express Oct3/4, Sox2, Klf4, and c-Myc, while the NIH-supported team forced adult skin cells to express OCT4, SOX2, NANOG, and LIN28. The genes were all chosen for their known importance in maintaining the so-called "stemness" properties of stem cells. In both reports, the adult skin cells are thus reprogrammed into human iPS cells that demonstrate important characteristics of pluripotency, including the ability to differentiate into cells characteristic of each embryonic germ layer. The techniques reported by these research teams will enable scientists to generate patient-specific and disease-specific human stem cell lines for laboratory study, and to test potential drugs on human cells in culture. However, these human iPS cells are not yet suitable for use in transplantation medicine. The current techniques use viruses that could generate tumors or other undesirable mutations in cells derived from iPS cells. Scientists are now working to accomplish reprogramming in adult human cells without using potentially dangerous viruses. Cell 131:861–72, laboratory of S. Yamanaka, 2007 Nov 30; Science 318:1917–1920, laboratory of J. Thomson, 2007 Dec 21.
Scientists Generate Stem Cell Line from Patient with Lou Gehrig's DiseasePrivately funded scientists report successfully generating stem cells from a patient with an inherited form of Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS). Starting with skin cells from the patient, the scientists used viruses to insert factors to reprogram the adult skin cells into induced pluripotent stem cells (iPSC) (see Human Skin Cells Reprogrammed). Once they had generated an ALS-iPSC line, the scientists coaxed the cells into becoming the type of motor neurons that are destroyed in ALS. These iPSC-derived motor neurons carry genes responsible for ALS and hold great potential for investigating the ALS disease process in human cells. Scientists are still uncertain whether the iPSC-derived motor neurons will degenerate in the same way as the patient's naturally occurring motor neurons. Ongoing experiments are comparing healthy motor neurons to the ALS-iPSC–derived motor neurons. If the iPSC-derived motor neurons show signs of ALS-like degeneration, they will be invaluable for observing events in the course of the ALS disease process and for testing potential ALS drugs on human cells in the laboratory before the drugs are used in humans. Science advance online publication, laboratory of K. Eggan. 2008 July 31.
Adult Stem Cell Lines Created for 10 Additional Human DiseasesOne week after the report of induced pluripotent stem cells (iPS cells) generated from an Amyotrophic Lateral Sclerosis (ALS) patient, NIH-funded scientists reported generating iPS cell lines carrying 10 additional human diseases. The new iPS cell lines were generated from individuals with Duchenne muscular dystrophy, Becker muscular dystrophy, juvenile-onset (type 1) diabetes, Parkinson's disease, Huntington's disease, Down syndrome, ADA severe combined immunodeficiency, Shwachman-Bodian-Diamond syndrome, Gaucher disease, and a carrier of Lesch-Nyhan Syndrome. As before, scientists must still determine whether the relevant cell types derived from these lines demonstrate symptoms of the diseases. For example—do muscle cells from the Duchenne MD iPS line behave as they do in individuals with the disease? The cell lines are capable of long term self-renewal in culture, thus providing a potentially endless supply of material for study of disease processes and testing of potential drugs on human cells. Scientists may now be able to generate and compare iPS lines from individuals with the same disease but different symptoms—a potential insight into what is due to inheritance and what is due to environment. Cell advance online publication, laboratories of C. Cowan, K. Hochedlinger, G. Daley. 2008 August 6.
Another Safety Improvement for Generating Induced Pluripotent Stem Cells (iPSCs)Scientists funded by the Juvenile Diabetes Research Foundation, the United Kingdom, and Canada reprogrammed mouse and human fibroblasts without using potentially dangerous viruses. For both types of fibroblasts, the reprogramming genes and an inducible transcription factor (can be used to turn expression on and off) were carried into the cells by naked DNA sequences. The naked DNA carriers also contained marking sequences that are targeted and "cut out" by specific enzymes. Using these special carriers, the scientists were able to insert reprogramming genes, turn them on for a specific period of time, and then remove the reprogramming genes and the transcription factor by adding the specific enzyme that zeroes in on and cuts out its targets. This method has several benefits: temporary expression of the reprogramming genes, the ability to remove inserted DNA after reprogramming is accomplished, use of a single carrier for all four reprogramming genes, and carriers' seeming increased resistantance to "silencing," or being inactivated (which could explain the higher efficiency as compared to other non-viral carriers).
This method has some potential drawbacks. Insertion of the reprogramming factors is random and could still temporarily interfere with an important gene. Part of the carrier DNA is often left behind even after removal. The DNA cuts made at the DNA removal site are not always repaired correctly. The PiggyBac method used for some of the experiments employs a transposon, or "jumping gene." Jumping genes are known to cause human diseases such as muscular dystrophy or hemophilia, as well as increase susceptibility to cancer. The bottom line: These methods are another step toward improving our ability to reprogram cells and increasing our understanding of reprogramming. However, these methods could still pose a danger to human health if derivatives of these cells are used to treat humans. The cells generated by this method are a valuable research tool and provide useful means to screen drugs and establish human disease models in culture. Nature advance online publication, laboratory of A. Nagy; Nature advance online publication, laboratory of K. Woltjen. 2009 Mar 6.