Document Detail

Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells.
MedLine Citation:
PMID:  15625106     Owner:  NLM     Status:  MEDLINE    
Implants of collagen-fibronectin gels containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVECs) induce the formation of human endothelial cell (EC)/murine vascular smooth muscle cell (VSMC) chimeric vessels in immunodeficient mice. Microfil casting of the vasculature 60 d after implantation reveals highly branched microvascular networks within the implants that connect with and induce remodeling of conduit vessels arising from the abdominal wall circulation. Approximately 85% of vessels within the implants are lined by Bcl-2-positive human ECs expressing VEGFR1, VEGFR2, and Tie-2, but not integrin alpha(v)beta(3). The human ECs are seated on a well formed human laminin/collagen IV-positive basement membrane, and are surrounded by mouse VSMCs expressing SM-alpha actin, SM myosin, SM22alpha, and calponin, all markers of contractile function. Transmission electron microscopy identified well formed EC-EC junctions, chimeric arterioles with concentric layers of contractile VSMC, chimeric capillaries surrounded by pericytes, and chimeric venules. Bcl-2-HUVEC-lined vessels retain 70-kDa FITC-dextran, but not 3-kDa dextran; local histamine rapidly induces leak of 70-kDa FITC-dextran or India ink. As in skin, TNF induces E-selectin and vascular cell adhesion molecule 1 only on venular ECs, whereas intercellular adhesion molecule-1 is up-regulated on all human ECs. Bcl-2-HUVEC implants are able to engraft within and increase perfusion of ischemic mouse gastrocnemius muscle after femoral artery ligation. These studies show that cultured Bcl-2-HUVECs can differentiate into arterial, venular, and capillary-like ECs when implanted in vivo, and induce arteriogenic remodeling of the local mouse vessels. Our results support the utility of differentiated EC transplantation to treat tissue ischemia.
David R Enis; Benjamin R Shepherd; Yinong Wang; Asif Qasim; Catherine M Shanahan; Peter L Weissberg; Michael Kashgarian; Jordan S Pober; Jeffrey S Schechner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-29
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-12     Completed Date:  2005-02-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  425-30     Citation Subset:  IM    
Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, and Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
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MeSH Terms
Capillary Permeability
Cell Differentiation
Endothelial Cells / transplantation*
Hindlimb / blood supply
Histamine / pharmacology
Ischemia / therapy*
Microscopy, Electron
Neovascularization, Physiologic*
Proto-Oncogene Proteins c-bcl-2 / genetics*
Transduction, Genetic
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Necrosis Factor-alpha; 51-45-6/Histamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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