In vitro Hepatic Differentiation of Human Mesenchymal Stem Cells

TLDR

The study investigates whether human mesenchymal stem cells can differentiate into functional hepatocyte‑like cells in vitro. MSCs were isolated from bone marrow and umbilical cord blood, characterized for mesodermal potential, and then differentiated into hepatocyte‑like cells using a two‑step protocol with hepatocyte growth factor and oncostatin M over four weeks. The differentiated cells exhibited albumin production, glycogen storage, urea secretion, LDL uptake, and phenobarbital‑inducible CYP activity, demonstrating functional hepatocyte‑like properties and supporting MSCs as a potential source for hepatic tissue engineering, while their broad differentiation capacity suggests a need to revise the MSC definition. Hepatology 2004;40:1275‑1284.

Abstract

This study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from embryonic mesoderm, are able to differentiate into functional hepatocyte–like cells in vitro . MSCs were isolated from human bone marrow and umbilical cord blood, and the surface phenotype and the mesodermal multilineage differentiation potentials of these cells were characterized and tested. To effectively induce hepatic differentiation, we designed a novel 2–step protocol with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time–dependent manner. Differentiated cells further demonstrated in vitro functions characteristic of liver cells, including albumin production, glycogen storage, urea secretion, uptake of low–density lipoprotein, and phenobarbital–inducible cytochrome P450 activity. In conclusion , human MSCs from different sources are able to differentiate into functional hepatocyte–like cells and, hence, may serve as a cell source for tissue engineering and cell therapy of hepatic tissues. Furthermore, the broad differentiation potential of MSCs indicates that a revision of the definition may be required. (Hepatology 2004;40:1275-1284.)