Iranian Journal of Medical Sciences

Document Type: Review Article


1 Department of Anatomical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran


There are several differentiation methods for mesenchymal stem cells (MSCs) into hepatocyte-like cell. Investigators reported various hepatic differentiation protocols such as modifying culturing conditions or using various growth factors/cytokines. In this literature review, we compared different MSCs extraction and isolation protocols from Wharton’s jelly (WJ) and explored various MSCs differentiation methods.
Various protocols have been recommended for MSCs isolated from WJ, such as enzymatic, enzymatic-explant, and explant methods. In the explant method, valuable time is wasted, but the cost and biological contaminations are reduced and the number of isolated cells is high. However, other features, such as immune phenotype and multiline-age differentiation capacity, do not differ from other methods. There are also several differentiation methods for hepatocyte-like cell including the induction of MSC by cytokines and growth factors, and the differentiation of MSC in 2- and 3-dimensional matrix (2D and 3D). Among several cytokines, hepatocyte growth factor (HGF) and fibroblast growth factor (FGF) are essential. In the early stage of the differentiation, 2D culture is useful, and in the development stage, 3D culture system with HGF and FGF cytokines are more effective in the process of differentiation. Some studies have used 3D culture system in biocompatible scaffolds, such as alginate, collagen, gelatin, and peptide-Gly-Leu-amide (PGLA).
In conclusion, Wharton’s jelly-Mesenchymal stem cells (WJ-MSCs) can be considered as an appropriate source for hepatocyte differentiation. Moreover, we introduced the explant method as the most effective protocol. This review attempted to highlight factors in hepatocyte differentiation, but the most effective protocol is not still unknown.