Transdifferentiation of bone marrow-derived cells into hepatic lineage cells: the methods of transdifferentiation in vitro and hepatic cells transplantation in vivo

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Evidence that bone marrow cells have trans-differencing potential to hepatocytes have been described in recent reports. However, the molecular mechanism underlying this phenomenon is unclear. To address this issue, we investigated the parameters involved in the trans-differentiation ob bone marrow cells into hepatic lineage. (Methods) Mouse BM cells were cultured in a collagen gel without or with growth factors, including basic fibroblast growth factor. The expression of hepatocyte-specific markers, cholangiocyte-specific marker and liver-enriched transcription factors was identified by RT-PCR and immunohistochemistry. (Results) Basic fibroblast growth factor was found to be the most effective for inducing albumin in cultured BM cells. Furthermore, on stimulation of basic fibroblast growth factor, BM cells were found to express other hepatocyte-specific markers and a cholangiocyte-specific marker. This conversion was found to be associated with the induction of transcription factors including hepatocyte nuclear factors and GATA family proteins. (Conclusion) We established an in vitro culture system in which mouse bone marrow cells could trans-differentiate to hepatic lineage cells in response to growth factors. In particular, basic fibroblast growth factor has the ability to induce the trans-differentiation into hepatic lineage cells from BM cells.