Endothelial implants provide long-term control of vascular repair in a porcine model of arterial injury.
Cell culture and animal data support the role of endothelial cells and endothelial-based compounds in regulating vascular repair after injury. We describe a long-term study in pigs in which the biological and immunological responses to endothelial cell implants were investigated 3 months after angioplasty, approximately 2 months after the implants have degraded. Confluent porcine or bovine endothelial cells grown in polymer matrices were implanted adjacent to 28 injured porcine carotid arteries. Porcine and bovine endothelial cell implants significantly reduced experimental restenosis compared to control by 56 and 31%, respectively. Host humoral responses were investigated by detection of an increase in serum antibodies that bind to the bovine or porcine cell strains used for implantation. A significant increase in titer of circulating antibodies to the bovine cells was observed after 4 days in all animals implanted with xenogeneic cells. Detected antibodies returned to presurgery levels after Day 40. No significant increase in titer of antibodies to the porcine cells was observed during the time course of the experiment in animals implanted with porcine endothelial cells. No implanted cells, Gelfoam, or focal inflammatory reaction could be detected histologically at any of the implant sites at 90 days. These data suggest that tissue-engineered endothelial cell implants may provide long-term control of vascular repair after injury, rather than simply delaying lesion formation and that allogeneic implants are able to provide a greater benefit than xenogeneic implants.
Nugent
H M
HM
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA. enugent@curis.com
Edelman
E R
ER
D000818:Animals; D000917:Antibody Formation; D020212:Carotid Artery Injuries / Q000276:immunology / Q000473:pathology* / Q000601:surgery*; D002404:Catheterization; D002417:Cattle; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005781:Gelatin Sponge, Absorbable; D006490:Hemostatics; D006965:Hyperplasia; D008297:Male; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology* / Q000637:transplantation*; D014945:Wound Healing / Q000276:immunology*
D006490:Hemostatics