Liver failure is a critical disease for which regenerative therapies are still being explored. The major limitation in the use of a clinical grade, viable cell-based therapy approach is the scarce availability of sufficient number of in-vitro differentiated hepatocyte-like cells (HLC) that can induce regeneration and ameliorate liver injury. Here, we report for the first time an approach to engineer HLCs using sera of hyperbilirubin patients that act as a reservoir of differentiation factor. Utilizing our humanized approach, mesenchymal stem cells (hMSC) derived from umbilical cord tissue were transdifferentiated into HLC using patient-derived serum along with dimethyl sulfoxide (DMSO). We studied the effects of serum on the proliferation, cell cycle analysis, and apoptosis of hMSC by various differentiation combinations. We optimized the hepatic transdifferentiation ability of hMSC with hyperbilirubin serum treatment for a period of 7 days. Assessment of HLC functionalities was shown by quantifying the HLC spent medium for albumin and urea secretions. Transplantation of HLC in an acute liver injury (ALI) rat model showed an effective improvement in the liver function and histological changes in the liver. The results of this study suggest that hMSC-derived HLC using humanized hepatogenic serum holds a promising potential for cell transplantation, as an efficient therapy modality for liver failure in humans.
Keywords: acute liver injury (ALI); differentiation; hepatocytes-like cells (HLC); hepatogenic serum; mesenchymal stem cells (MSC).
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