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

Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center and Institute for NanoBioTechnology, and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 07/2013; 110(31). DOI: 10.1073/pnas.1306562110
Source: PubMed


The success of tissue regenerative therapies is contingent on functional and multicellular vasculature within the redeveloping tissue. Although endothelial cells (ECs), which compose the vasculature's inner lining, are intrinsically able to form nascent networks, these structures regress without the recruitment of pericytes, supporting cells that surround microvessel endothelium. Reconstruction of typical in vivo microvascular architecture traditionally has been done using distinct cell sources of ECs and pericytes within naturally occurring matrices; however, the limited sources of clinically relevant human cells and the inherent chemical and physical properties of natural materials hamper the translational potential of these approaches. Here we derived a bicellular vascular population from human pluripotent stem cells (hPSCs) that undergoes morphogenesis and assembly in a synthetic matrix. We found that hPSCs can be induced to codifferentiate into early vascular cells (EVCs) in a clinically relevant strategy amenable to multiple hPSC lines. These EVCs can mature into ECs and pericytes, and can self-organize to form microvascular networks in an engineered matrix. These engineered human vascular networks survive implantation, integrate with the host vasculature, and establish blood flow. This integrated approach, in which a derived bicellular population is exploited for its intrinsic self-assembly capability to create microvasculature in a deliverable matrix, has vast ramifications for vascular construction and regenerative medicine.

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    • "The phase image of the vascular network and a close-up image of the vascular vessel cross-section were shown here. Adapted with permission from Ref. [105]. Copyright 2013, United States National Academy of Sciences. "
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    • "hPSC-derived endothelial progenitors and endothelial cells may provide building blocks for the establishment of in vitro disease models for screening and development of drugs to treat these diseases. Functionality of hPSC-derived endothelial cells has been shown using in vitro cell culture platforms and in vivo animal models (Adams et al., 2013; Kusuma et al., 2013; Orlova et al., 2014; Samuel et al., 2013; Wang et al., 2007). Similar to other somatic cells derived from hPSCs, differentiated CD31 + endothelial cells exhibited functional heterogeneity (Rufaihah et al., 2013). "
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