Enhanced hepatogenic differentiation of bone marrow derived mesenchymal stem cells on liver ECM hydrogel.

ABSTRACT

Bone marrow derived mesenchymal stem cells (BM-MSC) is a promising alternative cell source to primary hepatocytes because of their ability to differentiate into hepatocyte-like cells. However, their inability to differentiate efficiently and potential to turn into myofibroblasts restrict their applications. This study developed a plate coating from the liver extracellular matrix (ECM) and investigated its ability in facilitating the BM-MSCs proliferation, hepatic differentiation, and hepatocyte-specific functions during in vitro culture. After 28-day culture, BM-MSCs on the ECM coating showed hepatocyte-like morphology, and certain cells took up low-density lipoprotein. Synthesis of albumin, urea, and anti-alpha-fetoprotein, as well as expression of certain hepatic markers, in cells cultured on ECM were higher than cells cultured on non-coated and Matrigel-coated plates. mRNA levels of CYP3A4, albumin, CK18, and CYP7A1 in cells on ECM coating were significantly higher than cells cultured on the non-coating environment. In conclusion, viability and hepatogenic differentiation of BM-MSCs cultured on both Matrigel and ECM coating were significantly enhanced compared with those cultured on non-coated plates. Moreover, the liver ECM coating induced additional metabolic functions relative to the Matrigel coating. The liver ECM hydrogel preserves the natural composition, promotes simple gelling, induces efficient stem cell hepatogenic differentiation, and may have uses as an injectable intermedium for hepatocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A 106A 829-838, 2018.