NDLI: Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.

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Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.

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Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Van Poll, Daan Parekkadan, Biju Cho, Cheul H. Berthiaume, François Nahmias, Yaakov Tilles, Arno W. Yarmush, Martin L.
Description	Country affiliation: United States Author Affiliation: van Poll D ( Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospitals for Children, Boston, MA, USA.)
Abstract	UNLABELLED: Orthotopic liver transplantation is the only proven effective treatment for fulminant hepatic failure (FHF), but its use is limited because of organ donor shortage, associated high costs, and the requirement for lifelong immunosuppression. FHF is usually accompanied by massive hepatocellular death with compensatory liver regeneration that fails to meet the cellular losses. Therefore, therapy aimed at inhibiting cell death and stimulating endogenous repair pathways could offer major benefits in the treatment of FHF. Recent studies have demonstrated that mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promote tissue repair in models of myocardial infarction, acute kidney failure, and stroke through the action of trophic secreted molecules. In this study, we investigated whether MSC therapy can protect the acutely injured liver and stimulate regeneration. In a D-galactosamine-induced rat model of acute liver injury, we show that systemic infusion of MSC-conditioned medium (MSC-CM) provides a significant survival benefit and prevents the release of liver injury biomarkers. Furthermore, MSC-CM therapy resulted in a 90% reduction of apoptotic hepatocellular death and a three-fold increment in the number of proliferating hepatocytes. This was accompanied by a dramatic increase in the expression levels of 10 genes known to be up-regulated during hepatocyte replication. Direct antiapoptotic and promitotic effects of MSC-CM on hepatocytes were demonstrated using in vitro assays. CONCLUSION: These data provide the first clear evidence that MSC-CM therapy provides trophic support to the injured liver by inhibiting hepatocellular death and stimulating regeneration, potentially creating new avenues for the treatment of FHF.
File Format	HTM / HTML
ISSN	02709139
Issue Number	5
Volume Number	47
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2008-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Carcinoma, Hepatocellular Pathology Physiopathology Surgery Liver Failure Liver Neoplasms Liver Regeneration Physiology Mesenchymal Stem Cell Transplantation Alanine Transaminase Blood Animals Aspartate Aminotransferases Cell Death Humans Liver Function Tests Male Mesenchymal Stromal Cells Rats Rats, Sprague-dawley Transplantation, Heterologous Journal Article Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Hepatology

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