The HUVEC/Matrigel assay: an in vivo assay of human angiogenesis suitable for drug validation.
The future ability to manipulate the growth of new blood vessels (angiogenesis) holds great promise for treating ischemic disease and cancer. Several models of human in vivo angiogenesis have been described, but they seem to depend on transgenic support and have not been validated in a therapeutic context. Here, we describe an in vivo assay that mimics human angiogenesis in which native human umbilical vein-derived endothelial cells are suspended in a liquid laminin/collagen gel (Matrigel), injected into immunodeficient mice, and develop into mature, functional vessels that vascularize the Matrigel plug in the course of 30 d. Moreover, we demonstrate how to target this process therapeutically by sustained delivery of the angiogenesis inhibitor endostatin from subcutaneously implanted microosmotic pumps.
Skovseth
Dag K
DK
Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway.
Küchler
Axel M
AM
Haraldsen
Guttorm
G
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D004268:DNA-Binding Proteins / Q000235:genetics; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D043169:Endostatins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007279:Injections, Subcutaneous; D007797:Laminin; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011509:Proteoglycans; D014471:Umbilical Veins / Q000166:cytology
D043925:Angiogenesis Inducing Agents; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D043169:Endostatins; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; C499308:Rag2 protein, mouse; C059485:matrigel; D003094:Collagen