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.

 


STEM CELL RESEARCH



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.

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


Abstract
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 Genetic Heterogeneity in Therapy-Naïve Synchronous Primary Breast Cancers and Their Metastases. Clin Cancer Res. 2017 Aug 01;23(15):4402-4415 Authors: Ng CKY, Bidard FC, Piscuoglio S, Geyer FC, Lim RS, de Bruijn I, Shen R, Pareja F, Berman SH, Wang L, Pierga JY, Vincent-Salomon A, Viale A, Norton L, Sigal B, Weigelt B, Cottu P, Reis-Filho JS Abstract Purpose: Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition and genetic alterations, but it is unclear whether these differences stem from the selective pressures of the metastatic process, the systemic therapies, or both. We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy.Experimental Design: Up to two anatomically distinct core biopsies of primary breast cancers and synchronous distant metastases from nine patients who presented with metastatic disease were subjected to high-depth whole-exome sequencing. Mutations, copy number alterations and their cancer cell fractions, and mutation signatures were defined using state-of-the-art bioinformatics methods. All mutations identified were validated with orthogonal methods.Results: Genomic differences were observed between primary and metastatic deposits, with a median of 60% (range 6%-95%) of shared somatic mutations. Although mutations in known driver genes including TP53, PIK3CA, and GATA3 were preferentially clonal in both sites, primary breast cancers and their synchronous metastases displayed spatial intratumor heterogeneity. Likely pathogenic mutations affecting epithelial-to-mesenchymal transition-related genes, including SMAD4, TCF7L2, and TCF4 (ITF2), were found to be restricted to or enriched in the metastatic lesions. Mutational signatures of trunk mutations differed from those of mutations enriched in the primary tumor or the metastasis in six cases.Conclusions: Synchronous primary breast cancers and metastases differ in their repertoire of somatic genetic alterations even in the absence of systemic therapy. Mutational signature shifts might contribute to spatial intratumor genetic heterogeneity. Clin Cancer Res; 23(15); 4402-15. ©2017 AACR. PMID: 28351929 [PubMed - indexed for MEDLINE]
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Related Articles Differentiation of umbilical cord mesenchymal stem cells into hepatocytes in comparison with bone marrow mesenchymal stem cells. Mol Med Rep. 2018 Jun 18;: Authors: Yu YB, Song Y, Chen Y, Zhang F, Qi FZ Abstract Mesenchymal stem cells (MSCs) are considered to be an ideal source for the cell therapy of end‑stage liver diseases. Umbilical cord (UC)‑MSCs can be obtained via a non‑invasive procedure and can be easily cultured, making them potentially superior candidates for cell transplantation when compared with MSCs from other sources. In the present study, UC‑MSCs were induced to differentiate into hepatocytes and were compared with bone marrow (BM)‑MSCs for their hepatic differentiation potential. UC‑MSCs showed significantly higher proliferation than BM‑MSCs. Under hepatic induction, UC‑MSCs and BM‑MSCs could differentiate into hepatocytes. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis revealed that a higher expression of the hepatocyte‑specific genes albumin, cytochrome P450 3A4 (CYP3A4), tyrosine‑aminotransferase, glucose‑6phosphate, α1 antitrypsin and α‑fetoprotein was detected in differentiated UC‑MSCs when compared with differentiated BM‑MSCs. The results of ELISA and western blotting were in accordance with those of RT‑qPCR. Theses results indicated that UC‑MSCs had higher hepatic differentiation potential than BM‑MSCs. Therefore, UC‑MSCs may be advantageous over BM‑MSCs for the treatment of end‑stage liver disease. PMID: 29916543 [PubMed - as supplied by publisher]
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