Chondrogenesis of Embryonic Stem Cell-Derived Mesenchymal Stem Cells Induced by TGF1 and BMP7 Through Increased TGF Receptor Expression and Endogenous TGF1 Production

For decades stem cells have proven to be invaluable to the study of tissue development. More recently, mesenchymal stem cells (MSCs) derived from embryonic stem cells (ESCs) (ESC-MSCs) have emerged as a cell source with great potential for the future of biomedical research due to their enhanced proliferative capability compared to adult tissue-derived MSCs and effectiveness of musculoskeletal lineage-specific cell differentiation compared to ESCs. We have previously compared the properties and differentiation potential of ESC-MSCs to bone marrow-derived MSCs. In this study, we evaluated the potential of TGF1 and BMP7 to induce chondrogenic differentiation of ESC-MSCs compared to that of TGF1 alone and further investigated the cellular phenotype and intracellular signaling in response to these induction conditions. Our results showed that the expression of cartilage-associated markers in ESC-MSCs induced by the TGF1 and BMP7 combination was increased compared to induction with TGF1 alone. The TGF1 and BMP7 combination upregulated the expression of TGF receptor and the production of endogenous TGFs compared to TGF1 induction. The growth factor combination also increasingly activated both of the TGF and BMP signaling pathways, and inhibition of the signaling pathways led to reduced chondrogenesis of ESC-MSCs. Our findings suggest that by adding BMP7 to TGF1-supplemented induction medium, ESC-MSC chondrogenesis is upregulated through increased production of endogenous TGF and activities of TGF and BMP signaling. J. Cell. Biochem. 118: 172-181, 2017. (c) 2016 Wiley Periodicals, Inc.