Liver transplantation is the gold standard treatment for end-stage liver failure and for numerous liver based inborn errors of metabolism. However, organ shortage remains a major limiting factor and alternative solutions are being examined in the liver therapy field. Liver cell transplantation has become the most promising alternative. Compared to liver transplantation, this procedure is less invasive, less expensive, and fully reversible. But it is still limited by cell viability, modest engraftment and tissue availability.
Increasing interest is carried to stem cells regarding the recent demonstration of their plasticity. Theoretical advantages of mesenchymal stem cells for tissue regenerative medicine are multiple: ease of harvest, proliferation capacity, efficiency of in vitro transfection and potential use of autologous cells. Despite encouraging results, key pitfalls remain while using stem cells-derived hepatocyte-like cells: low engraftment rate and no strong liver repopulation level in animal models.
To identify the differentiation plasticity of adult bone marrow mesenchymal stem cells (MSCs) into hepatocyte-like phenotypes, we used a co-culture model with hepatocytes. Furthermore, we investigated whether MSCs can protect the acutely injured hepatocytes, stimulate regeneration and restore the functions of hepatocytes.
This data have evidenced that the guided hepatic differentiation of MSCs is proportionate to the activity of co-cultured hepatocytes. The hepatogenic environment is crucial to MSCs differentiation. It evidenced the trans-differentiation potential of MSCs developing to the hepatocytes and restoration of the functions of acutely injured hepatocytes. Further future therapeutic application in hepatic regeneration will be focused on the created imitated niches for MSC to maintain the survival and functions of hepatocytes.
