Liver Disease Stem Cell Treatment

Liver Disease and Stem Cell Therapy at SIRM


Liver Disease and Stem Cell Treatment

Liver Disease and Stem Cell Treatment

What is Liver Disease?
The liver is under your ribs on the right hand side. The liver is the largest organ in the body and if the liver fails completely then untreated only 3-4 days to find a donor liver for a possible transplant.

Corrently there is no such thing as an artificial liver.

The liver not only produces many proteins it creates energy from our food. The liver removes waste products in our body and also removes unwanted drugs such as nicotine and alcohol.

The most common Liver conditions include infections such as hepatitis A, B, C, E, alcohol damage, fatty liver, cirrhosis, cancer, drug damage especially paracetamol (acetaminophen) and cancer drugs.


The liver does not have any pain nerves so liver disease can be unexpected.
Liver disease is commonly related to alcohol and diet problems.



Use of hepatocyte and stem cells for treatment of post-resectional liver failure: are we there yet?

Ezzat TM, Dhar DK, Newsome PN, Malagó M, Olde Damink SW.

2011 Jul;31(6):773-84. doi: 10.1111/j.1478-3231.2011.02530.x. Epub 2011 Apr 19.

HPB and Liver Transplantation Surgery, Royal Free Hospital, University College London, Pond Street, London, UK.

Post-operative liver failure following extensive resections for liver tumours is a rare but significant complication. The only effective treatment is liver transplantation (LT); however, there is a debate about its use given the high mortality compared with the outcomes of LT for chronic liver diseases.

Cell therapy has emerged as a possible alternative to LT especially as endogenous hepatocyte proliferation is likely inhibited in the setting of prior chemo/radiotherapy. Both hepatocyte and stem cell transplantations have shown promising results in the experimental setting; however, there are few reports on their clinical application.

This review identifies the potential stem cell sources in the body, and highlights the triggering factors that lead to their mobilization and integration in liver regeneration following major liver resections.

Therapeutic plasticity of stem cells and allograft tolerance.

Cytotherapy. 2011 May 10;

Authors: Sordi V, Piemonti L

Abstract Transplantation is the treatment of choice for many diseases that result in organ failure, but its success is limited by organ rejection. Stem cell therapy has emerged in the last years as a promising strategy for the induction of tolerance after organ transplantation. Here we discuss the ability of different stem cell types, in particular mesenchymal stromal cells, neuronal stem/progenitor cells, hematopoietic stem cells and embryonic stem cells, to modulate the immune response and induce peripheral or central tolerance.

These stem cells have been studied to explore tolerance induction to several transplanted organs, such as heart, liver and kidney. Different strategies, including approaches to generating tolerance in islet transplantation, are discussed here.

PMID: 21554176 [PubMed - as supplied by publisher]



Impaired function of bone marrow-derived endothelial progenitor cells in  murine liver fibrosis.

Biosci Trends. 2011 Apr;5(2):77-82

Authors: Shirakura K, Masuda H, Kwon SM, Obi S, Ito R, Shizuno T, Kurihara Y,  Mine T, Asahara T

Liver fibrosis (LF) caused by chronic liver damage has been considered as an  irreversible disease. As alternative therapy for liver transplantation, there  are high expectations for regenerative medicine of the liver.

Bone marrow (BM)-  or peripheral blood-derived stem cells, including endothelial progenitor cells  (EPCs), have recently been used to treat liver cirrhosis. We investigated the  biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were  subcutaneously injected with carbon tetrachloride (CCl4)  every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood  (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical  examination.

Assessments of EPC in the peripheral blood and BM were performed by  flow cytometry and EPC colonyforming assay, respectively, using purified MNCs  and BM c-KIT+, Sca-1+, and  Lin- (KSL) cells.

Liver tissues underwent histological  analysis with hematoxylin/eosin/Azan staining, and spleens were excised and  weighed. CCl4-treated mice exhibited histologically  bridging fibrosis, pseudolobular formation, and splenomegaly, indicating  successful induction of LF.

The frequency of definitive EPC-colony-forming-units  (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells  decreased significantly (p < 0.0001) in LF mice compared with control mice;  no significant changes in primitive EPC-CFU occurred in LF mice.

The frequency  of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF  mice compared with control mice. Together, these findings indicated the  existence of impaired EPC function and differentiation in BM-derived EPCs in LF  mice and might be related to clinical LF.

PMID: 21572251 [PubMed - in process]

Related Articles Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients. PLoS One. 2017;12(9):e0185210 Authors: Chen CT, Liu CY, Yu YB, Liu CJ, Hsiao LT, Gau JP, Chiou TJ, Liu JH, Liu YC Abstract Chronic graft-versus-host-disease (cGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362). Poor outcome, in terms of overall survival (OS), were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2.037, 95% confidence interval [CI] 1.123-3.696, P = 0.019). In multivariate analysis, male gender (HR 4.004, P = 0.042) and chronic hepatitis C virus (HCV) infection status (HR 19.087, P < 0.001) were statistically significant risk factors for scores of 3 liver cGvHD. Our results indicate that liver cGvHD with scores of 3 has a grave prognosis following allo-HSCT, and that HCV carrier status and male are risk factors. Early recognition of this devastating complication might help in prompt immunosuppressive therapy and reducing late poor outcome. PMID: 28934311 [PubMed - in process]
Related Articles Exosomes from Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells (hiPSC-MSCs) Protect Liver against Hepatic Ischemia/ Reperfusion Injury via Activating Sphingosine Kinase and Sphingosine-1-Phosphate Signaling Pathway. Cell Physiol Biochem. 2017 Sep 21;43(2):611-625 Authors: Du Y, Li D, Han C, Wu H, Xu L, Zhang M, Zhang J, Chen X Abstract BACKGROUND/AIMS: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury, as well as the underlying mechanisms. METHODS: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated. The serum levels of transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as histological changes were examined. Primary hepatocytes and human hepatocyte cell line HL7702 were used to test whether exosomes could induce hepatocytes proliferation in vitro. In addition, the expression levels of proliferation markers (proliferation cell nuclear antigen, PCNA; Phosphohistone-H3, PHH3) were measured by immunohistochemistry and Western blot. Moreover, SK inhibitor (SKI-II) and S1P1 receptor antagonist (VPC23019) were used to investigate the role of sphingosine kinase and sphingosine-1-phosphate-dependent pathway in the effects of hiPSC-MSCs-Exo on hepatocytes. RESULTS: hiPSCs were efficiently induced into hiPSC-MSCs that had typical MSC characteristics. hiPSC-MSCs-Exo had diameters ranging from 100 to 200 nm and expressed exosome markers (Alix, CD63 and CD81). After hiPSC-MSCs-Exo administration, hepatocyte necrosis and sinusoidal congestion were markedly suppressed in the ischemia/reperfusion injury model, with lower histopathological scores. The levels of hepatocyte injury markers AST and ALT were significantly lower in the treatment group compared to control, and the expression levels of proliferation markers (PCNA and PHH3) were greatly induced after hiPSC-MSCs-Exo administration. Moreover, hiPSC-MSCs-Exo also induced primary hepatocytes and HL7702 cells proliferation in vitro in a dose-dependent manner. We found that hiPSC-MSCs-Exo could directly fuse with target hepatocytes or HL7702 cells and increase the activity of sphingosine kinase and synthesis of sphingosine-1-phosphate (S1P). Furthermore, the inhibition of SK1 or S1P1 receptor completely abolished the protective and proliferative effects of hiPSC-MSCs-Exo on hepatocytes, both in vitro and in vivo. CONCLUSIONS: Our results demonstrated that hiPSC-MSCs-Exo could alleviate hepatic I/R injury via activating sphingosine kinase and sphingosine-1-phosphate pathway in hepatocytes and promote cell proliferation. These findings represent a novel mechanism that potentially contributes to liver regeneration and have important implications for new therapeutic approaches to acute liver disease. PMID: 28934733 [PubMed - as supplied by publisher]

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