Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: Implications for cell-based vascular therapy

Conclusion: Endothelial progenitor cells (EPC) may play an important role in reestablishing endothelial integrity of injured vessels. They thus may inhibit neointimal hyperplasia and improve patency of small caliber bioprosthetic grafts. Summary: Blood-borne endothelial cells from adult bone marrow have properties of EPCs. EPCs recruited at the sites of injury may differentiate into mature endothelial cells and participate in tissue repair. A method for isolation and expression of EPCs from blood yielding sufficient numbers for potential therapeutic applications was developed. Identification of EPCs was facilitated by retrovial insertion of the bacterial LacZ gene into the EPC. In a rabbit model, balloon-injured carotid arteries and 4-mm internal diameter polytetrafluoroethylene (PTFE) grafts were evaluated for the ability of seeded EPC cells to lead to endothelialization of denuded vessels and graft segments. Endothelialization was confirmed by using staining of luminal surfaces for the endothelial cell marker CD31. In the balloon-injured carotid arteries, 4 days after EPC seeding, >70% of the luminal surface was covered with LacZ-positive cells. No Lac-Z positive cells were visible after 4 weeks. Endothelial cell coverage at 4 days after seeding was 60% of the luminal surface in seeded arteries versus less than 5% in control vessels. EPC transplantation reduced neointimal thickening at 2 weeks (P < .05). At 4 weeks, in the PTFE grafts seeded with EPCs, 40% to 60% of the luminal area was covered by endothelial cells versus <5% in control grafts. Comment: The current data may spawn a new round of research in endothelial seeding of bioprosthetic grafts, this time using bone marrow\Nderived EPCs as a source of endothelial cells. Such grafts could serve as arterial substitutes or as delivery mechanisms for cell-based therapy.