In vitro differentiation of human bone marrow mesenchy-mal stem cells into hepatocyte-like cells

Orthotropic liver transplantation [OLT] is the final procedure of both end stage and metabolic liver diseases. Hepatocyte transplantation is an alternative for OLT, but the sources of hepatocytes are limited. Bone marrow mesenchymal stem cells [BM-MSCs] can differentiate into hepatocyte-like cells and are a potential alternative source for hepatocytes. We aimed to investigate the differentiation potential of BM-MSCs into hepatocyte-like cells. Human BM-MSCs from a healthy donor were cultured and differentiated into hepatocyte-like cells. We investigated the expression of hepatocyte-specific markers in MSC-derived hepatocyte-like cells [MSC-HLC[s]] and evaluated their functionality using metabolic assays. MSC-HLCs expressed hepatocyte-specific markers at both mRNAand protein levels. In addition, the cells had the ability to uptake low density lipoprotein [LDL], clear ammonia, secrete albumin, and store glycogen. MSC-HLCs were transplanted into a familial hypercholesteromia patient. Human MSCs can be differentiated into partially functional hepatocyte-like cells. Thus, they could be a potential source for cell therapy in liver disorders

[ role of ultraweb nano-fibrillar substrates in the differentiation of in vitro mouse bone marrow mesenchymal stem cell-derived hepatocyte-like cells]

To study the impact of ultraweb nano-fibrillar substrates on in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells into hepatocyte-like cells. For a duration of up to 36 days, mouse bone marrow mesenchymal stem cells [MSCs] were cultured on an artificial basement membrane containing ultraweb nanofiber [nano+] and plates [nano] coated with Matrigel and used growth and differentiating factors for hepatogenic differentiation. Then, to study the impact of nanofibers on hepatocyte differentiation, mRNA expressions for liver-specific genes [CK7, AFP, FOXa2, ALB, CYP1a1, HNF4a] were analyzed using real-time PCR, and ultrastructures of differentiated cells were evaluated using scanning and transmission electron microscope. Both experimental groups expressed mRNA of liver-specific genes in a time dependent manner. However, mRNA expression trends of liver-specific genes, especially those of FOXa2 and HNF4a, were better in the nano+ culture as compared to the nanoculture [p<0.05]. Furthermore, the ultrastructures of differentiated cells in the 36 day-old nano+ culture were more mature as compared to those of the nanogroup. The results suggest that topographical properties of the extracellular matrices produced by ultraweb nanofibers are effective for the in vitro reproduction of more differentiated MSC-derived hepatocyte-like cells