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 Diminazene aceturate alleviated lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice. Biomed Pharmacother. 2018 Feb;98:142-148 Authors: Ge P, Yao X, Li J, Jiang R, Dai J, Zhang L Abstract Diminazene aceturate (DIZE) has been widely used as an antiprotozoal agent, but recent studies have revealed its anti-inflammatory activities. In the present study, the potential effects of DIZE on lethal inflammatory disorder were investigated in a mouse model with lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis. The results indicated that treatment with DIZE suppressed LPS/D-Gal-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated histopathological damage in liver and improved the survival rate of the experimental animals, these effects were accompanied with inhibited expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Treatment with DIZE also inhibited the activation of caspase-3, -8, -9, reduced the level of cleaved caspase-3, suppressed the phosphorylation of c-jun-N-terminal kinase (JNK) and decreased the count of TUNEL-positive cells. These data suggests that DIZE might have potential value in the prevention of inflammation-based lethal inflammatory liver disorders. PMID: 29253761 [PubMed - indexed for MEDLINE]
Related Articles In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis. World J Gastroenterol. 2017 Dec 14;23(46):8152-8168 Authors: Zhang GZ, Sun HC, Zheng LB, Guo JB, Zhang XL Abstract AIM: To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS: A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS: We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION: Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. PMID: 29290652 [PubMed - indexed for MEDLINE]
Related Articles Mesenchymal stem cell transplantation improves chronic colitis-associated complications through inhibiting the activity of toll-like receptor-4 in mice. BMC Gastroenterol. 2018 Aug 13;18(1):127 Authors: Niu GC, Liu L, Zheng L, Zhang H, Shih DQ, Zhang X Abstract BACKGROUND: A variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) have been shown to play a potential role in the therapy of IBD. This study was designed to investigate the effect and mechanism of MSCs on chronic colitis-associated hepatobiliary complications using mouse chronic colitis models induced by dextran sulfate sodium (DSS). METHODS: DSS-induced mouse chronic colitis models were established and treated with MSCs. Severity of colitis was evaluated by disease activity index (DAI), body weight (BW), colon length and histopathology. Serum lipopolysaccharide (LPS) levels were detected by limulus amebocyte lysate test (LAL-test). Histology and liver function of the mice were checked correspondingly. Serum LPS levels and bacterial translocation of mesenteric lymph nodes (MLN) were detected. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-17A (IL-17A), Toll receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6) and nuclear factor kappa B (NF-κB) were detected by immunohistochemical staining, western blot analysis and real-time PCR, respectively. RESULTS: The DSS-induced chronic colitis model was characterized by reduced BW, high DAI, worsened histologic inflammation, and high levels of LPS and E. coli. Liver histopathological lesions, impaired liver function, enhanced proteins and mRNA levels of TNF-α, IFN-γ, IL-1β, IL-17A, TLR4, TRAF6 and NF-κB were observed after DSS administration. MSCs transplantation markedly ameliorated the pathology of colon and liver by reduction of LPS levels and proteins and mRNA expressions of TNF-α, IFN-γ, IL-1β, IL-17A, TLR4, TRAF6 and NF-κB. CONCLUSIONS: MSCs can improve chronic colitis-associated hepatobiliary complications, probably by inhibition of enterogenous endotoxemia and hepatic inflammation through LPS/TLR4 pathway. MSCs may represent a novel therapeutic approach for chronic colitis-associated hepatobiliary complications. PMID: 30103680 [PubMed - in process]
Related Articles Antifibrotic potential of bone marrow‑derived mesenchymal stem cells in biliary atresia mice. Mol Med Rep. 2018 Aug 03;: Authors: Lei J, Chai Y, Xiao J, Hu H, Liu Z, Xiao Y, Yi L, Huang J, Xiang T, Zhang S Abstract Biliary atresia (BA) is a rare and severe disease that affects infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and mortality if untreated. Bone marrow‑derived mesenchymal stem cells (BMMSCs) have been considered as a promising therapy in fibrotic diseases. The aim of the present was to investigate the anti‑fibrotic roles of BMMSC transplantation in a BA mouse model. Mouse BA models were established by Rhesus rotavirus administration to neonatal mice. The results revealed that the liver enzyme and bilirubin metabolism levels, and the levels of the oxidative stress marker malondialdehyde (MDA) and the fibrosis marker were all increased in the BA model, while the liver tissue levels of superoxide dismutase and glutathione peroxidase were reduced. The hematoxylin and eosin and Masson's trichrome staining revealed severe liver fibrosis and collagen accumulation in BA livers. However, these indicators were all reversed once the BA mice were administered the BMMSC inoculation. In conclusion, the present study demonstrated the anti‑fibrotic potential of BMMSCs in BA mice, which may provide a novel approach to ameliorate the fibrotic response in BA patients. PMID: 30106103 [PubMed - as supplied by publisher]

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