Abstract
The shortage of donor livers and hepatocytes is a major limitation of liver transplantation. Thus, generation of hepatocyte-like cells may provide alternative choice for therapeutic applications. In this study, we developed a new method to establish hepatocytes from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cell lines named WJMSCs-SUT1 and WJMSCs-SUT2 under hypoxic condition. This new method could rapidly drive both WJ-MSCs cell lines into hepatic lineage within 18 days. The achievement of hepatogenic differentiation was confirmed by the characterization of both phenotypes and functions. More than 80% MSCs-derived hepatocyte-like cells (MSCDHCs) achieved functional hepatocytes including hepatic marker expressions both at gene and protein levels, glycogen storage, low-density lipoprotein uptake, urea production, and albumin secretion. This study highlights the establishment of new hepatogenic induction protocol under hypoxic condition in order to mimic hypoxic microenvironment in typical cell physiology. In conclusion, we present a simple, high-efficiency, and time saving protocol for the generation of functional hepatocyte-like cells from WJ-MSCs in hypoxic condition. The achievement of this method may overcome the limitation of donor hepatocytes and provides a new avenue for therapeutic value in cell-based therapy for life-threatening liver diseases, regenerative medicine, toxicity testing for pharmacological drug screening, and other medical related applications.
Highlights
Orthotopic liver transplantation has been shown to be an effective treatment for patients with end stage of liver dysfunction
We developed a new method to induce Wharton’s jelly-derived mesenchymal stem cells (WJ-mesenchymal stem cells (MSCs)) cell lines, WJMSCs-SUT1, and WJMSCsSUT2, into hepatic lineage followed by characterization of the MSCs-derived hepatocyte-like cells (MSCDHCs) at both cellular and molecular levels
We observed morphological changing from fibroblastic cells of WJ-MSCs into polygonal round cells of hepatocytes feature
Summary
Orthotopic liver transplantation has been shown to be an effective treatment for patients with end stage of liver dysfunction This treatment is limited by the shortage of donor organs. MSCs can be extensively expanded in vitro, due to effective cryopreservation and being easy to access from various sources such as bone marrow, adipose tissue, amniotic fluid, umbilical cord Wharton’s jelly, and placenta [3,4,5,6]. These make MSCs become a good stem cell candidate for therapeutic purpose in clinical applications
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