Three-dimensional growth of iPS cell-derived smooth muscle cells on nanofibrous scaffolds

Induced pluripotent stem cells (iPSCs) have been considered as the major component for personalized regenerative medicine. However, the potential of iPSCs in constructing tissue-engineered (TE) blood vessels has not been exploited. In the present study, we generated mouse iPSCs with the combination of over-expression of 4 iPS factors and knock-down of p53 gene. The established iPSCs were then directed to differentiate into smooth muscle cells (SMCs) with the treatment of 10−5 m all-trans retinoid acid (RA). The vehicle dimethyl sulfoxide (DMSO) treatment served as a spontaneous differentiation control. The differentiated cells were then cultured on three-dimensional (3D) macro-porous nanofibrous (NF) poly(l-lactide) (PLLA) scaffolds in vitro. Our data showed that the expression of SMC specific marker genes, including myocardin, smoothelin, SM22α and SMMHC, were higher for the group induced by RA than for the group treated by DMSO, while pluripotent marker gene expression was repressed by the RA-treatment. Upon subcutaneous implantation, the implanted cells maintained the SMC phenotype. In conclusion, the data suggest that iPSCs-derived SMCs can be an important cell source for personalized vascular tissue engineering applications.