In vivo Formation of Complex Microvessels Lined by Human Endothelial Cells in an Immunodeficient Mouse

We have identified conditions for forming cultured human umbillical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fib...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-08, Vol.97 (16), p.9191-9196
Main Authors: Schechner, Jeffrey S., Nath, Anjali K., Zheng, Lian, Kluger, Martin S., Christopher C. W. Hughes, Sierra-Honigmann, M. Rocio, Lorber, Marc I., Tellides, George, Kashgarian, Michael, Alfred L. M. Bothwell, Pober, Jordan S.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bcl-2 protein
Biological Sciences
Capillaries - cytology
Capillaries - ultrastructure
Cells
Cells, Cultured
Coculture Techniques
Collagens
Cultured cells
Electron microscopy
Endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - ultrastructure
Gels
Human umbilical vein endothelial cells
Humans
Medical research
Mice
Mice, SCID
Microscopy, Electron
Microvessels
Renovations
Rodents
Science
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Summary:We have identified conditions for forming cultured human umbillical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize into cords with early lumena by 24 h and then apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display HUVEC-lined thin-walled microvessels within the gel 31 days after implantation. Retroviral-mediated overexpression of a caspase-resistant Bcl-2 protein delays HUVEC apoptosis in vitro for over 7 days. Bcl-2-transduced HUVEC produce an increased density of HUVEC-lined perfused microvessels in vivo compared with untransduced or control-transduced HUVEC. Remarkably, Bcl-2- but not control-transduced HUVEC recruit an ingrowth of perivascular smooth-muscle α -actin-expressing mouse cells at 31 days, which organize by 60 days into HUVEC-lined multilayered structures resembling true microvessels. This system provides an in vivo model for dissecting mechanisms of microvascular remodeling by using genetically modified endothelium. Incorporation of such human endothelial-lined microvessels into engineered synthetic skin may improve graft viability, especially in recipients with impaired angiogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.150242297