Characterization and Proteomic Profiling of Hepatocyte-like Cells Derived from Human Wharton's Jelly Mesenchymal Stromal Cells: De Novo Expression of Liver-Specific Enzymes

Liver transplantation is the only therapeutic option for patients affected by end-stage liver disease (ESLD), but its feasibility is restricted by the shortage of donated organs. Stem cell therapy could represent a valid treatment option for these conditions. In particular, the mesenchymal stromal cells derived from the human umbilical cord matrix (WJ-MSCs), thanks to their specific features, can be considered good candidates for liver tissue repair and regeneration. We found that the WJ-MSCs differentiate in hepatocyte-like cells (HLCs) using a differentiation protocol that resembles the in vivo liver morphogenesis. We also showed that HLCs acquired mature hepatic functions and maintained their intrinsic hypoimmunogenicity, a key feature to avoid rejection in the host. Moreover, thanks to proteomic analysis, we highlighted several hepatic proteins in HLCs, demonstrating that these cells could be valid candidates for the treatment of ESLD.