Characterization of hepatic markers in human Wharton's Jelly-derived mesenchymal stem cells

Abstract

Stem cell technology could offer a unique tool to develop human-based in vitro liver models that are applicable for testing of potential liver toxicity early during drug development. In this context, recent research has indicated that human Wharton's Jelly-derived mesenchymal stem cells (hWJs) represent an interesting stem cell population to develop human hepatocyte-like cells. Here, an in-depth analysis of the expression of liver-specific transcription factors and other key hepatic markers in hWJs is evaluated at both the mRNA and protein level. Our results reveal that transcription factors that are mandatory to acquire and maintain an adult hepatic phenotype (HNF4A and HNF1A), as well as adult hepatic markers (ALB, CX32, CYP1A1, CYP1A2, CYP2B6 and CYP3A4) are not expressed in hWJs with the exception of K18. On the contrary, transcription factors involved in liver development (GATA4, GATA6, SOX9 and SOX17) and liver progenitor markers (DKK1, DPP4, DSG2, CX43 and K19) were found to be highly expressed in hWJs. These findings provide additional indication that hWJs could be a promising stem cell source to generate hepatocyte-like cells necessary for the development of a functional human-based in vitro liver model.

Keywords: 4′,6-diamidino-2-phenylindole; ACTB; AFP; ALB; Adult stem cells; B2M; CX; CYP; DAPI; DKK; DMEM-LG; DPP; DSG; Dulbecco’s modified eagle medium-low glucose; EGF; FBS; FGF; FOX; GAPDH; GJ; HEPs; HMBS; HNF; Hepatocyte; K; KRT; Liver development; MSCs; ND; ONECUT; PBS; PFA; SOX; UBC; Umbilical cord; Wharton’s Jelly; albumin; beta-2-microglobulin; beta-actin; connexin; cytochrome P450; desmoglein; dickkopf; dipeptidyl-peptidase; epidermal growth factor; fetal bovine serum; fibroblast growth factor; forkhead box; gap junction; glyceraldehyde 3-phosphate dehydrogenase; hADSCs; hASCs; hBMSCs; hSKPs; hWJs; hepatocyte nuclear factor; human Wharton’s Jelly-derived mesenchymal stem cells; human adipose tissue-derived stromal cells; human adult stem cells; human bone marrow-derived stromal cells; human hepatocytes; human skin-derived precursor cells; hydroxy-methylbilane synthase; keratin; mesenchymal stem cells; not significantly detected; onecut homeobox; paraformaldehyde; phosphate buffered saline; qPCR; quantitative real-time reverse transcriptase polymerase chain reaction; sex determining region Y-box; ubiquitin C; α-foetoprotein.