Tissue engineered perivascular endothelial cell implants regulate vascular injury.
Molecular biomaterial engineering permits in vivo transplantation of cells and tissues, offering the promise of restoration of physiologic control rather than pharmacologic dosing with isolated compounds. We engrafted endothelial cells on Gelfoam biopolymeric matrices with retention of viability, normal growth kinetics, immunoreactivity, and biochemical activity. The production of heparan sulfate proteoglycan and inhibition of basic fibroblast growth factor binding and activity by engrafted cells were indistinguishable from endothelial cells grown in culture. Perivascular implantation of Gelfoam-endothelial cell scaffolds around balloon-denuded rat carotid arteries reduced intimal hyperplasia 88.1%, far better than the isolated administration of heparin, the most effective endothelial mimic compound. In concert with a reduction in intimal area, cell proliferation was reduced by > 90%. To our knowledge, there have been no previous reports of extravascular cell implants controlling vasculoproliferative disease. Tissue engineered cells offer the potential for potent methods of vascular growth regulation and insight into the complex autocrine-paracrine control mechanisms within the blood vessel wall.
Nathan
A
A
Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge 02139, USA.
Nugent
M A
MA
Edelman
E R
ER
D000818:Animals; D001704:Biopolymers; D016466:CHO Cells; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology* / Q000637:transplantation; D005781:Gelatin Sponge, Absorbable; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D051381:Rats; D014652:Vascular Diseases / Q000628:therapy
D001704:Biopolymers