NDLI: In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse

Content Provider	PubMed Central
Author	Schechner, Jeffrey S. Nath, Anjali K. Zheng, Lian Kluger, Martin S. Hughes, Christopher C. W. Rocio, Sierra-honigmann M. Lorber, Marc I. George, Tellides Michael, Kashgarian Bothwell, Alfred L. M. Pober, Jordan S.
Copyright Year	2000
Abstract	We have identified conditions for forming cultured human umbilical 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.
Related Links	http://dx.doi.org/10.1073/pnas.150242297
Ending Page	9196
Page Count	6
Starting Page	9191
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-08-01
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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