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Differentiation of neural crest stem cells in response to matrix stiffness and TGF-β1 in vascular regeneration.

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The neural crest stem cells derived from human induced pluripotent stem cells (iPSC-NCSCs) are a valuable autologous cell source for tissue engineering and regenerative medicine. In this study, we investigated… Click to show full abstract

The neural crest stem cells derived from human induced pluripotent stem cells (iPSC-NCSCs) are a valuable autologous cell source for tissue engineering and regenerative medicine. In this study, we investigated how iPSC-NCSCs could be regulated to regenerate arteries by microenvironmental factors, including the physical factor of matrix stiffness, and the chemical factor of transforming growth factor beta-1 (TGF-β1). We found that, compared to soft substrate, stiff substrate drove iPSC-NCSC differentiation into smooth muscle cells (SMCs), which was further enhanced by TGF-β1. To investigate the regulatory role of TGF-β1 in vivo, we fabricated vascular grafts composed of electrospun nanofibrous scaffolds, collagen gel, iPSC-NCSCs and TGF-β1, and implanted them into athymic rats. The results showed that TGF-β1 significantly promoted extracellular matrix (ECM) synthesis and increased mechanical strength of vascular grafts. This study presents a proof of concept that iPSC-NCSCs can be used as a promising autologous cell source for vascular regeneration when combined with physical and chemical engineering.

Keywords: crest stem; matrix; ipsc ncscs; neural crest; stem; stem cells

Journal Title: Stem cells and development
Year Published: 2019

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