Intraportal injection of porcine multipotent mesenchymal stromal cells augments liver regeneration after portal vein embolization.

UNLABELLED: Portal vein embolization (PVE) can be used prior to liver surgery to increase the volume of the remaining liver tissue after an extensive resection. However, the application of PVE is limited and new strategies to augment liver regeneration by cellular therapy are promising alternatives. MATERIALS AND METHODS: The influence of syngeneic multipotent mesenchymal stromal cells (MSC) on liver regeneration was analysed after the ligation of the right portal vein branches in a porcine model, closely mimicking the situation of human surgery. Liver regeneration was monitored by ultrasonography, immunohistological analysis and serum biochemistry. RESULTS: The volume of the contra-lateral, non-ligated liver lobe increased in all piglets after portal vein ligation. This hyperplasia occurred earlier and was more pronounced in those piglets receiving MSC infusions as compared to non-treated controls. Biochemical liver function was stable in all pigs. Only solitary transplanted MSC were detected in recipient livers two weeks after the infusion. CONCLUSION: The infusion of porcine MSC into the portal vein in a setting of liver regeneration after surgical resection leads to accelerated and augmented hyperplasia. This effect is most likely due to bystander effects of the transplanted MSC.

No contribution of multipotent mesenchymal stromal cells to liver regeneration in a rat model of prolonged hepatic injury.

Multipotent mesenchymal stromal (MS) cells from adult bone marrow are a cell population that can be expanded to large numbers in culture. MS cells might be differentiated toward hepatocytes in vitro and thus are promising candidates for therapeutic applications in vivo. The efficacy of bone marrow-derived MS cells 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 (CCl(4)) or allyl alcohol (AA) with and without retrorsine (R) pretreatment. MS cells or hepatocytes of wild-type F344 rats were injected into dipeptidyl 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) compared with the R/CCl(4) treatment group (MCS = 18). No hepatocyte engraftment was outlined following post-transplant CCl(4) 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 MS cells 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 MS cell transplantation. Data from the present study indicate that a well-defined population of MS cells 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.