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Tissue-Specific Stem Cells |
1 Department of Surgery, University of Regensburg, Regensburg, Germany
* To whom correspondence should be addressed. E-mail: felix.popp{at}klinik.uni-regensburg.de.
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Abstract |
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Multipotent mesenchymal stromal cells (MSC) from adult bone marrow are a cell population that can be expanded to large numbers in culture. MSC might be differentiated towards hepatocytes in vitro and, thus, are promising candidates for therapeutic applications in vivo.
The efficacy of bone marrow-derived MSC versus hepatocytes to contribute to liver regeneration was compared in a rat model of prolonged toxic hepatic injury. Liver damage was induced by injection of carbon tetrachloride (CCl4) or allyl alcohol (AA) with and without retrorsine (R) pretreatment. MSC respectively hepatocytes of wild-type F344 rats were injected into dipetidyl peptidase IV (DPPIV) deficient syngeneic rats.
Hepatocyte chimerism was higher after intraportal hepatocyte transplantation in the R/AA group (mean maximal cluster size, MCS=21 cells) as compared to the R/CCl4 treatment group (MCS=18). No hepatocyte engraftment was outlined following post-transplant CCl4 injection only, whereas mere AA injection resulted in small clusters of donor-derived hepatocytes (MCS=2). Intraparenchymal injection of hepatocytes was associated with a MCS=11 after R/AA treatment and a MCS=6 after AA administration alone. Redistribution of MSC to the liver was shown after intraportal and intraparenchymal injection. In contrast to hepatocyte transplantation, however, donor derived DPPIV positive cells could not be demonstrated in any recipient after MSC transplantation.
Data from the present study indicate that a well-defined population of MSC obtained according to established standard protocols does not differentiate into hepatocytes in vivo when transplanted under regenerative conditions, in which the application of hepatocytes results in stable hepatic engraftment.
Key Words. multipotent mesenchymal stromal cells, liver regeneration, hepatocyte transplantation, DPPIV rat model, transdifferentiation in vivo
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