Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation.

ABSTRACT

BACKGROUND: Although different strategies have been established for hepatic differentiation of mesenchymal stromal cells (MSC), further studies are required to define an efficient strategy to produce hepatocytes from stem cells and uncover the mechanisms of hepatic differentiation. METHODS: Bone marrow mesenchymal stromal cells (BMMSC), isolated from ICR mice, were induced by fetal liver-conditioned medium from different developmental stages, embryonic days (ED) 9.5, 11.5 and 13.5 and newborn (1 day). Differentiated cells were characterized by morphologic changes, liver-specific gene expression at mRNA and/or protein levels and in vitro functional features. RESULTS: BMMSC morphologically became epithelioid and binucleated after 7 days' exposure to fetal liver-conditioned medium from ED13.5, expressed liver-specific genes (AFP, HNF-3beta, TTR, CK18, ALB and CK19) at mRNA and/or protein levels and acquired in vitro functions characteristic of liver cells, including glycogen storage, urea production and albumin secretion. Conditioned medium derived from fetal liver at ED13.5 was most efficient on hepatic differentiation of BMMSC compared from the other three developmental stages. DISCUSSION: The present study not only provides a high-performance strategy for hepatic differentiation from BMMSC, but also implies liver at different developmental stages might secrete different types of cytokines that have diverse effects on hepatic differentiation, which could support further investigation to provide insight into fundamental processes that govern development and regeneration of the liver.