Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）,...Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.展开更多
基金supported by NIH R01 DE14190(HX),R21 DE22625(HX)and R01 HL-073781(LC)the University of Maryland School of Dentistry startup fund(HX)
文摘Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.
