Transdifferentiation Of Mouse BM MSCs Into Hepatocyte-like Cells

At present, trans-differentiation of adult stem cells is a hot topic in cell biology. Committed tissue stem/progenitor cells possess multipotent differentiation. They can not only differentiated into cell types of the same embryonic layer, but also tran-differentiated into cell types of different embryonic layer. But the majority studies of the hepatic stem cell have been focused on in vivo and minority studies are in vitro. Bone marrow mesenchymal stem cells (BM MSCs) have self-renewal capacity and show multipotency of differentiation. A number of studies have readily demonstrated that, under proper treatments or in a suitable microenvironment, BM-derived cells express various liver specific genes at the mRNA level in vitro, indicating that BM may be an alternative source of hepatocyte progenitors. To establish an effective method for inducing mouse bone marrow mesenchymal stem cells to differentiate into hepatocytes, we isolated MSCs from mouse bone marrow and cultured them in Iscove's Modified Dulbecco's medium supplemented with 10% new bovine serum (NBS), 20 ng/mL hepatocyte growth factor (HGF), 10 ng/mL fibroblast growth factor-4 (FGF-4) and 10 ng/ml oncostatin m (OSM) for 20 days' induction. In groups induced by three cytokines after 20 days, BM MSCs showed characteristic of hepatocytes. On day 10, AFP mRNA of MSCs could be detected by RT-PCR, and the expression of AFP decreased on day 20. CK18 mRNA could also be detected from day 15 to day 20. Albumin and TAT can be detected on day 20 by RT-PCR. Immunofluorescence assay for CK18, albumin showed positive staining reaction on day 20. Differentiated cells further demonstrated these cells also acquired functional characteristics of hepatocytes that they can store glycogen. In conclusion, HGF, FGF-4 and Oncostatin M (OSM) can be successfully employed to induce hepatic transdifferentiation from mouse BM cells. Thus the present work may serve as a novel model for the study of mechanism involved in mesenchymal stem cell transdifferentiation, and a resource for the cytotherapy of liver disease with BM cells.