The influence of fibroblast growth factor 4 on hepatogenic capacity of Wharton's jelly mesenchymal stromal cells.

Wharton's jelly mesenchymal stromal cells (WJ-MSCs) derived from human umbilical cords could be an appropriate candidate for hepatocyte replacement therapy. Improvement of the efficiency of the cell expression of liver specific genes can be considered in finding new transplantation resources. The present study aimed to differentiate WJ-MSCs toward hepatocyte-like cells on collagen film in the presence of hepatogenic factors, including fibroblast growth factor 4 (FGF4), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1). MSCs derived from Wharton's jelly explants were characterized by flow cytometry. Then, the cells were cultured in the presence of hepatogenic media with or without FGF4 on 2D collagen films for 21 days. The expression of liver-specific genes was evaluated by real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. The functional assays were performed by Periodic Acid-Schiff (PAS) staining and Indocyanin Green (ICG) uptake. The cultures pre-exposed to FGF4 expressed higher levels of endodermal markers, such as albumin, compared to the control cultures. Also, cytokeratin 18 expression was significantly increased in FGF4-treated cells. However, the expression level of other liver-specific markers was not influenced by exposure to hepatogenic media with or without FGF4. In conclusion, it was demonstrated that FGF4 could induce the differentiation of WJ-MSCs toward endoderm. Despite the morphological changes and increase in PAS reaction, WJ-MSCs could not differentiate into hepatocytes by hepatogenic media consisting of IGF-1.