Journal
BIOMATERIALS
Volume 32, Issue 19, Pages 4369-4375Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.02.049
Keywords
Induced pluripotent stem cells; Smooth muscle cells; Scaffolds; Vascular tissue engineering
Funding
- Cardiovascular Center at University Michigan
- National Institutes of Health [HL092421, HL068878, DE015384, DE017689]
- AHA [09SDG2260023]
- Richard H. Kingery Endowed Collegiate Professorship
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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, SM22 alpha 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. (C) 2011 Elsevier Ltd. All rights reserved.
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