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IDL - International Digital Library ISSN: IDL
Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org
IDL - International Digital Library 1 | P a g e Copyright@IDL-2017
Stem Cell Therapy in Liver Cirrhosis
Ghassemi A
Associate Professor of Pediatric Hematology & Oncology & Stem Cell Transplantation, Hematology and Oncology Ward, Faculty
of Medicine, Mashhad University of Medical Sciences
Abstract
Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients
with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative
damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the
potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to
provide a renewable source of cells for transplantation.
The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct
cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest
stages of human development and disease modeling using human cells.
Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in
liver regeneration
I. INTRODUCTION
cell Stem cells is applied to cells from many different sources with many different functions and phenotypes and is a
general descriptive term, Stem cells characteristics are regenerate identical cells, transplant ability, maintain the ability
to proliferate and multipotentiality, but can be stimulated to leave differentiate into specific cell types and this self
renewal cycle. Stem cells are divided four categories: totipotent, pluripotent, multipotent or unipotent. Totipotent cells
are capable of giving rise to any cell in the embryo and extra embryonic tissue. Stem cell populations that may give
rise to only limited cell types are multipotent. In this article, we review the potential for stem cell therapies to treat
liver cirrhosis, MSCs cells are reprogrammed as useful sources of cells that can be change to liver cell for treatment of
cirrhosis but pathological implication and autologous bone marrow stem cell therapy for cirrhosis are still to be
elucidated and clinical trials that required before this cell transplantation must be performed in Large-scale controlled
to becomes a regular therapy.
II. PRACTICE POINTS
 lifestyle changes—stop or reduce drinking, stop smoking,
 lose weight (if obese) † nutrition intervention—adequate diet (calories and composition)
 drug therapy—as yet no FDA-approved therapy for alcoholic cirrhosis or alcoholic hepatitis.
IDL - International Digital Library ISSN: IDL
Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org
IDL - International Digital Library 2 | P a g e Copyright@IDL-2017
 some CAM agents hold promise for cirrhosis; pentoxyfilline appears effective for alcoholic hepatitis .
 liver transplantation corrects liver failure and disease complications
III. STEM CELL
In cirrhosis Currently, Most of studies have been performed in rodent models of liver injury using either
whole/fractionated bone marrow transplantation/injection or peripheral blood stem cells obtained through the
administration of growth factors, because of the increasing shortage of livers for transplantation, Scientists attempted
to performed experiments for optimizing and demonstration of the supposed ability of adult bone marrow stem cells to
differentiate into mature cells other than blood cells in different adult tissues and functioning hepatocytes .
IV. THE ROLE OF LIVER TRANSPLANTATION
There have been multiple recent studies and reviews concerning liver transplantation in patients with severe alcoholic
cirrhosis.150–154 There is a well-documented organ shortage for liver transplantation and there are serious ethical
issues concerning this controversial area that have precipitated these studies. Hepatitis C and ALD are the two major
reasons for liver transplantation in the USA. Data clearly demonstrate that patients transplanted for ALD do (short-
and long-term) as well as patients transplanted for hepatitis C or other types of liver disease. However, alcoholic
hepatitis clearly is not an indication for liver transplantation at the current time. Virtually all centres require that
alcoholic patients undergo formal psychiatric evaluation and treatment prior to transplantation. Many centres impose a
‘six month rule’ of abstinence before being considered for orthotopic liver transplantation (OLT); however, most
centres also show some flexibility with this rule. It is unusual for ALD alone to be the cause of graft failure. The
majority of patients with ALD are not listed for liver transplantation for multiple reasons including continued alcohol
consumption, improvement of liver function with abstinence, lack of interest, etc. Patients with ALD appear to have a
higher incidence of certain malignancies of the upper airway and upper digestive tract. Therefore, these patients should
be screened for these processes prior to transplantation and monitored carefully .
V. POST-TRANSPLANTATION.
Data suggest that, following transplantation, patients who had ALD and those who were transplanted for other reasons
consume alcohol at relatively similar rates, although those who had ALD may consume greater amounts. The rate of
alcohol use increases over time for all transplant recipients. Some centres use multi-stage screening processes with risk
stratification to select patients with low rates of recidivism. Clearly, more studies are required to refine our predictive
capabilities for both recidivism and non-compliance. Quality of life appears to improve after liver transplantation due
to any aetiology, although those with non-alcohol related aetiologies may improve more.
CONCLUSION
Studies suggested that multipotent stem cells may exist among bone marrow cells; and bone marrow stem cells
contribute to liver regeneration after injury [54]. In vitro studies reported that bone marrow MSCs can inhibit collagen
IDL - International Digital Library ISSN: IDL
Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org
IDL - International Digital Library 3 | P a g e Copyright@IDL-2017
synthesis and induce apoptosis in hepatic satellites cells [60] and studies on animal showed the anti-fibrotic effects of
MSCs injected through peripheral vein [61]. According to the potential for stem cells to differentiate or their paracrine
secretion, stem cell transplantation has become an attractive alternative therapeutic method for the treatment of
patients with liver disease, at least, at a temporary support of hepatic function until a liver becomes available for organ
transplantation.
In this review, the potential of the BMC to differentiate into hepatocytes and other cell lineages has already been
reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into
hepatocytes, and we demonstrated, MSCs cells are reprogrammed as useful sources of cells with hepatic potential for
cirrhosis therapy but pathological implication and autologous bone marrow cell therapy for cirrhosis are still to be
elucidated and clinical trials that required before this cell transplantation must be performed in Large-scale controlled
to becomes a regular therapy
ACKNOWLEDGMENTS
We would like to thank all people who participate in this study.
REFERENCES
[1]. Lorenzini S, Andreone P (2007) Stem Cell Therapy for Human Liver Cirrhosis: A Cautious Analysis of the
Results. Stem Cells 25(9): 2383-2384.
[2]. Tsochatzis EA, Bosch J, Burroughs AK (2014) Liver cirrhosis. Lancet 383(9930): 1749-1761. [3]. Vig P, Russo
FP, Edwards RJ, Tadrous PJ, Wright NA, Thomas HC, et al. (2006) The source of parenchymal regeneration after
chronic hepatocellular liver injury in mice. Hepatology 43(2): 316-324.
[4]. Dalakas E, Newsome PN, Harrison DJ, Plevris JN (2005) Hematopoietic stem cell trafficking in liver injury.
FASEB J 19(10): 1225-1231.
[5]. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, et al. (2002) Bone marrow cells adopt the phenotype of
other cells by spontaneous cell fusion. Nature 416(6880): 542-545.
[6]. Ying QL, Nichols J, Evans EP, Smith AG (2002) Changing potency by spontaneous fusion. Nature 416(6880):
545-548.
[7]. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, et al. (2003) Cell fusion is the principal source of bone-
marrow-derived hepatocytes. Nature 422(6934): 897-901.
[8]. Houlihan DD, Newsome PN (2008) Critical Review of Clinical Trials of Bone Marrow Stem Cells in Liver
Disease. Gastroenterology 135(2): 438- 450.
[9]. Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, et al. (2007) Sox2: a possible
driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol 20(4): 474-481.
[10]. Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, et al. (2009) Functional evidence that the self-renewal
gene NANOG regulates human tumor development. Stem Cells 27(5): 993-1005.
[11]. Driesch H (1891) Entwicklungsmechanische Studien I. Der Wert der ersten beiden Furchungszellen in der
Echinodermenentwickelung Experimentelle Erzeugung von Teil und Doppelbildungen. Ztschr f Wiss Zool 53: 160-
183.
IDL - International Digital Library ISSN: IDL
Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org
IDL - International Digital Library 4 | P a g e Copyright@IDL-2017
[12]. Farber E (1956) Similarities in the sequence of early histological changes induced in the liver of the rat by
ethionine, 2-acetylamino-fluorene, and 3’-methyl-4- dimethylaminoazobenzene. Cancer Res 16(2): 142-148.
[13]. Dabeva MD, Shafritz DA (1993) Activation, proliferation, and differentiation of progenitor cells into
hepatocytes in the D-galactosamine model of liver regeneration. Am J Pathol 143(6): 1606-1620.
[14]. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, et al. (2002) Human autologous culture expanded bone
marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage
10(3): 199-206.
[15]. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of
transdifferentiation and modes of tissue repair – current views. Stem Cells 25(11): 2896-2902.
[16]. Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, et al. (1999) Autologous transplantation of bone marrow
cells improves damaged heart function. Circulation 100(19 Suppl II): 247-256. [17]. Kafienah W, Mistry S, Dickinson
SC, Sims TJ, Learmonth I, et al. (2007)

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Stem Cell Therapy in Liver Cirrhosis

  • 1. IDL - International Digital Library ISSN: IDL Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org IDL - International Digital Library 1 | P a g e Copyright@IDL-2017 Stem Cell Therapy in Liver Cirrhosis Ghassemi A Associate Professor of Pediatric Hematology & Oncology & Stem Cell Transplantation, Hematology and Oncology Ward, Faculty of Medicine, Mashhad University of Medical Sciences Abstract Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to provide a renewable source of cells for transplantation. The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest stages of human development and disease modeling using human cells. Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in liver regeneration I. INTRODUCTION cell Stem cells is applied to cells from many different sources with many different functions and phenotypes and is a general descriptive term, Stem cells characteristics are regenerate identical cells, transplant ability, maintain the ability to proliferate and multipotentiality, but can be stimulated to leave differentiate into specific cell types and this self renewal cycle. Stem cells are divided four categories: totipotent, pluripotent, multipotent or unipotent. Totipotent cells are capable of giving rise to any cell in the embryo and extra embryonic tissue. Stem cell populations that may give rise to only limited cell types are multipotent. In this article, we review the potential for stem cell therapies to treat liver cirrhosis, MSCs cells are reprogrammed as useful sources of cells that can be change to liver cell for treatment of cirrhosis but pathological implication and autologous bone marrow stem cell therapy for cirrhosis are still to be elucidated and clinical trials that required before this cell transplantation must be performed in Large-scale controlled to becomes a regular therapy. II. PRACTICE POINTS  lifestyle changes—stop or reduce drinking, stop smoking,  lose weight (if obese) † nutrition intervention—adequate diet (calories and composition)  drug therapy—as yet no FDA-approved therapy for alcoholic cirrhosis or alcoholic hepatitis.
  • 2. IDL - International Digital Library ISSN: IDL Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org IDL - International Digital Library 2 | P a g e Copyright@IDL-2017  some CAM agents hold promise for cirrhosis; pentoxyfilline appears effective for alcoholic hepatitis .  liver transplantation corrects liver failure and disease complications III. STEM CELL In cirrhosis Currently, Most of studies have been performed in rodent models of liver injury using either whole/fractionated bone marrow transplantation/injection or peripheral blood stem cells obtained through the administration of growth factors, because of the increasing shortage of livers for transplantation, Scientists attempted to performed experiments for optimizing and demonstration of the supposed ability of adult bone marrow stem cells to differentiate into mature cells other than blood cells in different adult tissues and functioning hepatocytes . IV. THE ROLE OF LIVER TRANSPLANTATION There have been multiple recent studies and reviews concerning liver transplantation in patients with severe alcoholic cirrhosis.150–154 There is a well-documented organ shortage for liver transplantation and there are serious ethical issues concerning this controversial area that have precipitated these studies. Hepatitis C and ALD are the two major reasons for liver transplantation in the USA. Data clearly demonstrate that patients transplanted for ALD do (short- and long-term) as well as patients transplanted for hepatitis C or other types of liver disease. However, alcoholic hepatitis clearly is not an indication for liver transplantation at the current time. Virtually all centres require that alcoholic patients undergo formal psychiatric evaluation and treatment prior to transplantation. Many centres impose a ‘six month rule’ of abstinence before being considered for orthotopic liver transplantation (OLT); however, most centres also show some flexibility with this rule. It is unusual for ALD alone to be the cause of graft failure. The majority of patients with ALD are not listed for liver transplantation for multiple reasons including continued alcohol consumption, improvement of liver function with abstinence, lack of interest, etc. Patients with ALD appear to have a higher incidence of certain malignancies of the upper airway and upper digestive tract. Therefore, these patients should be screened for these processes prior to transplantation and monitored carefully . V. POST-TRANSPLANTATION. Data suggest that, following transplantation, patients who had ALD and those who were transplanted for other reasons consume alcohol at relatively similar rates, although those who had ALD may consume greater amounts. The rate of alcohol use increases over time for all transplant recipients. Some centres use multi-stage screening processes with risk stratification to select patients with low rates of recidivism. Clearly, more studies are required to refine our predictive capabilities for both recidivism and non-compliance. Quality of life appears to improve after liver transplantation due to any aetiology, although those with non-alcohol related aetiologies may improve more. CONCLUSION Studies suggested that multipotent stem cells may exist among bone marrow cells; and bone marrow stem cells contribute to liver regeneration after injury [54]. In vitro studies reported that bone marrow MSCs can inhibit collagen
  • 3. IDL - International Digital Library ISSN: IDL Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org IDL - International Digital Library 3 | P a g e Copyright@IDL-2017 synthesis and induce apoptosis in hepatic satellites cells [60] and studies on animal showed the anti-fibrotic effects of MSCs injected through peripheral vein [61]. According to the potential for stem cells to differentiate or their paracrine secretion, stem cell transplantation has become an attractive alternative therapeutic method for the treatment of patients with liver disease, at least, at a temporary support of hepatic function until a liver becomes available for organ transplantation. In this review, the potential of the BMC to differentiate into hepatocytes and other cell lineages has already been reported. Several reports have also demonstrated the plasticity of hematopoietic stem cells to differentiate into hepatocytes, and we demonstrated, MSCs cells are reprogrammed as useful sources of cells with hepatic potential for cirrhosis therapy but pathological implication and autologous bone marrow cell therapy for cirrhosis are still to be elucidated and clinical trials that required before this cell transplantation must be performed in Large-scale controlled to becomes a regular therapy ACKNOWLEDGMENTS We would like to thank all people who participate in this study. REFERENCES [1]. Lorenzini S, Andreone P (2007) Stem Cell Therapy for Human Liver Cirrhosis: A Cautious Analysis of the Results. Stem Cells 25(9): 2383-2384. [2]. Tsochatzis EA, Bosch J, Burroughs AK (2014) Liver cirrhosis. Lancet 383(9930): 1749-1761. [3]. Vig P, Russo FP, Edwards RJ, Tadrous PJ, Wright NA, Thomas HC, et al. (2006) The source of parenchymal regeneration after chronic hepatocellular liver injury in mice. Hepatology 43(2): 316-324. [4]. Dalakas E, Newsome PN, Harrison DJ, Plevris JN (2005) Hematopoietic stem cell trafficking in liver injury. FASEB J 19(10): 1225-1231. [5]. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416(6880): 542-545. [6]. Ying QL, Nichols J, Evans EP, Smith AG (2002) Changing potency by spontaneous fusion. Nature 416(6880): 545-548. [7]. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, et al. (2003) Cell fusion is the principal source of bone- marrow-derived hepatocytes. Nature 422(6934): 897-901. [8]. Houlihan DD, Newsome PN (2008) Critical Review of Clinical Trials of Bone Marrow Stem Cells in Liver Disease. Gastroenterology 135(2): 438- 450. [9]. Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, et al. (2007) Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol 20(4): 474-481. [10]. Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, et al. (2009) Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 27(5): 993-1005. [11]. Driesch H (1891) Entwicklungsmechanische Studien I. Der Wert der ersten beiden Furchungszellen in der Echinodermenentwickelung Experimentelle Erzeugung von Teil und Doppelbildungen. Ztschr f Wiss Zool 53: 160- 183.
  • 4. IDL - International Digital Library ISSN: IDL Volume 1, Issue 1, FEB-2017 Available at: www.dbpuplications.org IDL - International Digital Library 4 | P a g e Copyright@IDL-2017 [12]. Farber E (1956) Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3’-methyl-4- dimethylaminoazobenzene. Cancer Res 16(2): 142-148. [13]. Dabeva MD, Shafritz DA (1993) Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration. Am J Pathol 143(6): 1606-1620. [14]. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, et al. (2002) Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 10(3): 199-206. [15]. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair – current views. Stem Cells 25(11): 2896-2902. [16]. Tomita S, Li RK, Weisel RD, Mickle DA, Kim EJ, et al. (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100(19 Suppl II): 247-256. [17]. Kafienah W, Mistry S, Dickinson SC, Sims TJ, Learmonth I, et al. (2007)