Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix

摘要

A bicellular vascular population derived from human pluripotent stem cells (hPSCs) undergoes morphogenesis and assembly in a synthetic hydrogel. It is shown that hPSCs can be induced to co-differentiate into early vascular cells (EVCs) in a clinically-relevant strategy dependent upon Notch activation. These EVCs mature into ECs and pericytes, and self-organize to form vascular networks in an engineered matrix. Upon in vivo implantation, multicellular human vascular networks are functionally perfused. Thus, a derived bicellular population is exploited for its intrinsic self-assembly capability to create functional microvasculature in a deliverable matrix.

主权项

1. A method for differentiating human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into early vascular cells (EVCs) in vitro, comprising the steps of:
plating a single-cell suspension of hESCs or hiPSCs onto a surface coated with suitable materials selected from the group consisting of type I collagen, fibronectin, and type IV collagen; adding culture medium; culturing the cells for several days; adding Vascular Endothelial Growth Factor (VEGF) and a transforming growth factor-beta (TGF-β) inhibitor to the culture medium; culturing the cells for several days; and harvesting the resulting EVCs, wherein said EVCs express CD73 and one or more of CD105 and CD146.