Exosomes from umbilical cords-derived mesenchymal stem cells (UC-MSCs-Ex) have been recognized as their ability to promote tissue regeneration in many animal models. However, the in vivo effects of UC-MSCs-Ex in small-for-size liver transplantation is lacking and its potential molecular mechanisms are still unknown. The aim of the present study was to determine whether UC-MSCs-Ex could promote liver regeneration after small-for-size liver transplantation. Firstly, rat small-for-size liver transplantation model was established, which is allogeneic 1/3 orthotopic liver transplantation. Subsequently, rats were divided into three groups randomly, which were administered in peripheral vein with PBS as control, UC-MSCs or UC-MSCs-Ex. Then, rats were sacrificed at different time-points. And the liver and serum were collected to assess liver function. We found that similar to UC-MSCs, UC-MSCs-Ex improved prognosis after small-for-size liver transplantation by improving liver function, increased remnant liver to weight ratio and the liver regenerative proliferation. Mechanistically, we found that increased liver regeneration effect is positively associated with Rho/ROCK signaling pathway, through Wetern blotting analysis. Furthermore, we used UC-MSCs-Ex with ripasudil, a Rho kinase inhibitor, to this model. And the results showed that the ability of UC-MSCs-Ex on promoting liver regeneration was reversed. In conclusion, these results indicate that by promoting cell proliferation, UC-MSCs-Ex mediated activation of Rho/ROCK signaling pathway could be a novel therapeutic strategy to treat small-for-size liver transplantation.

CITATION INFORMATION: Chen L., Zheng J., Cai J., Yao J., Zeng K., Zhang Y., Yang Y. Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells on Hepatocytes Proliferation after Small-for-Size Liver Transplantation via RHO/ROCK Pathway Am J Transplant. 2017;17 (suppl 3).

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