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Multi-stage endothelial differentiation and expansion of human pluripotent stem cells

Abstract

Human endothelial cells (ECs) have prospects for a wide range of clinical applications including cell-based therapies and tissue engineering and, hold tremendous potential for research in the fields of vascular development, drug discovery and disease modelling. Efficient and robust induction of ECs from human pluripotent stem cells (hPSCs) will serve as a renewable and indefinite source. However, distinct embryonic stem cell (hESC) and induced pluripotent stem (iPSC) cell lines respond differentially to the same microenvironmental signals. Developing an optimized differentiation methodology robust across multiple hPSC lines, including hiPSC lines derived from autologous patient specific cells remains a challenge in the field. We demonstrate a chemically defined multi-stage EC differentiation process across multiple hPSC lines. This method can generate highly purified populations of actively proliferating VE-Cadherin+ functional ECs in 30 days. There are a few published methods for efficient derivation large number of endothelial progenitor cells (EPC) within a week, but their maturation to definitive EC is tough, taking longer and requiring additional purification.

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