Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo

  title={Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo},
  author={Zack Z Wang and Patrick Au and Tong Chen and Ying Shao and Laurence Daheron and Hao Bai and Melanie Arzigian and Dai Fukumura and Rakesh K. Jain and David T. Scadden},
  journal={Nature Biotechnology},
We describe the differentiation of human embryonic stem (hES) cells into endothelial cells using a scalable two-dimensional method that avoids an embryoid-body intermediate. After transplantation into severe combined immunodeficient (SCID) mice, the differentiated cells contributed to arborized blood vessels that integrated into the host circulatory system and served as blood conduits for 150 d. 

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Methods for isolating purified proliferating populations of vascular endothelial cells from mouse embryonic stem cells from mESC using Flk-1 positive sorted cells, VEGF supplementation, and a rigorous manual selection technique required for endothelial cell purification and expansion are described.

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This review examines vasculogenesis and angiogenesis in murine embryoid bodies and discusses the promise of stem cell–based models for the study of human vascular development.

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The current status of directing hESCs to differentiate to vascular cells is reviewed and it is suggested that endothelial cells and SMCs derived from h ESCs can be used to engineer artificial vessels to repair damaged vessels and form vessel networks in engineered tissues.

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Embryonic stem cell models in vascular biology

Through culture of mouse embryonic stem cell, it is discovered that differentiating stem cells are highly amenable to analyzing biochemical and cell biologic processes that are independent of flow.

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A 10-day, two-stage process that recapitulates endothelial cell development, in which hPSCs first differentiate to endothelial progenitors that then generate functional endothelial cells and smooth muscle cells is demonstrated.

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The latest advances using the hESC model system are focused on, capitalizing on the well-established mouse embryonic stem cell model system, as a means to investigate the lineage commitment events underlying the early embryonic development of human hematopoietic and endothelial cells.

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Vascular diseases await translation of blood vessels engineered from stem cells

Current developments in the generation of vascular progenitor cells from hiPSCs and the assessment of their functional capacity in vivo are discussed, opportunities and challenges for the clinical translation of engineered vascular tissue, and modeling of vascular diseases using hiPSC-derived vascular progentitor cells are discussed.



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Molecular insights into the formation of new blood vessels are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated.

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The ability to induce formation of human embryoid bodies that contain cells of neuronal, hematopoietic and cardiac origins will be useful in studying early human embryonic development as well as in transplantation medicine.

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It is found that NO mediates mural cell coverage as well as vessel branching and longitudinal extension but not the circumferential growth of blood vessels in B16 murine melanomas.

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