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 miR-500a-3p promotes cancer stem cells properties via STAT3 pathway in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2017 Jul 27;36(1):99 Authors: Jiang C, Long J, Liu B, Xu M, Wang W, Xie X, Wang X, Kuang M Abstract BACKGROUND: miR-500a-3p has been demonstrated to be involved in the development, progression and metastasis in several human cancers. Constitutive activation of JAK/STAT3 signaling pathway has been reported to play an important role in the development and progression of hepatocellular carcinoma (HCC).The purpose of this study was to determine the biological roles and clinical significance of miR-500a-3p in HCC and to identify whether miR-500a-3p has an effect on the activity of JAK/STAT3 signaling in HCC. METHODS: miR-500a-3p expression was examined by real-time PCR in 8 paired HCC tissues and individual 120 HCC tissues respectively. Statistical analysis was performed to explore the clinical correlation between miR-500a-3p expression and clinicopathological features and overall and relapse-free survival in HCC patients. In vitro and in vivo assays were performed to investigate the biological roles of miR-500a-3p in HCC. The bioinformatics analysis, real-time PCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-500a-3p and its potential targets. Clinical correlation of miR-500a-3p with its targets was examined in HCC tissues. RESULTS: miR-500a-3p is dramatically elevated in HCC tissues and cells and high expression of miR-500a-3p correlates with poor overall and relapse-free survival in HCC patients. Upregulating miR-500a-3p enhances, while silencing miR-500a-3p suppresses, the spheroid formation ability, fraction of side population and expression of cancer stem cell factors in vitro and tumorigenicity in vivo in HCC cells. Our findings further reveal miR-500a-3p promotes the cancer stem cell characteristics via targeting multiple negative regulators of JAK/STAT3 signaling pathway, including SOCS2, SOCS4 and PTPN11, leading to constitutive activation of STAT3 signaling. Moreover, the inhibitory effects of anti-miR-500a-3p on cancer stem cell phenotypes and activity of STAT3 signaling were reversed by silencing SOCS2, SOCS4 and PTPN11 in miR-500a-3p-downexpressing cells, respectively. Clinical correlation of miR-500a-3p with the targets was examined in human HCC tissues. CONCLUSION: our results uncover a novel mechanism by which miR-500a-3p promotes the stemness maintenance of cancer stem cell in HCC, suggesting that silencing miR-500a-3p may serve as a new therapeutic strategy in the treatment of hepatocellular carcinoma. PMID: 28750679 [PubMed - indexed for MEDLINE]
Related Articles Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies. Cell Mol Gastroenterol Hepatol. 2018 Mar;5(3):426-439.e1 Authors: Underhill GH, Khetani SR Abstract In vitro models of the human liver are important for the following: (1) mitigating the risk of drug-induced liver injury to human beings, (2) modeling human liver diseases, (3) elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and (4) enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs), the gold standard for building human liver models, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrix-coated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli. The development of several engineering tools, such as cellular microarrays, protein micropatterning, microfluidics, biomaterial scaffolds, and bioprinting, now allow precise control over the cellular microenvironment for enhancing the function of both PHHs and induced pluripotent stem cell-derived human hepatocyte-like cells; long-term (4+ weeks) stabilization of hepatocellular function typically requires co-cultivation with liver-derived or non-liver-derived nonparenchymal cell types. In addition, the recent development of liver organoid culture systems can provide a strategy for the enhanced expansion of therapeutically relevant cell types. Here, we discuss advances in engineering approaches for constructing in vitro human liver models that have utility in drug screening and for determining microenvironmental determinants of liver cell differentiation/function. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues that need to be addressed. Overall, bioengineered liver models have significantly advanced our understanding of liver function and injury, which will prove useful for drug development and ultimately cell-based therapies. PMID: 29675458 [PubMed]

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