Periadventitial human stem cell treatment reduces vein graft intimal thickening in pig vein-into-artery interposition grafts

摘要

Background: Neointima formation and atherosclerosis compromise long-term graft patency in aortocoronary vein bypass grafts. We investigated the effect on neointima formation in porcine saphenous vein grafts of periadventitial application of immortalized human mesenchymal stem cells transduced with the gene for the peptide glucagon-like peptide-1, which have been shown to induce angiogenesis in previous studies and are protected from immune-mediated destruction by encapsulation in alginate microbeads (CellBeads). Methods and results: Periadventitial application of CellBeads was compared with alginate beads only or vehicle control in pig vein-into-artery interposition grafts. CellBeads significantly reduced neointimal area and total wall area compared with both control groups. This was associated with a significant increase in vein graft adventitial neoangiogenesis. CellBeads had no effect on vessel inward or outward remodeling and promoted adventitial collagen deposition. Alginate beads without stem cells reduced graft patency (6/15 grafts patent) versus CellBead-treated (6/7 grafts patent) or untreated grafts (7/8 grafts patent) (Fisher exact test, P = 0.052). There was no evidence of an inflammatory or cellular immune reaction to either the CellBeads or the alginate-only beads. Conclusions: Periadventitial treatment of porcine vein grafts with human stem cells inhibits neointima formation in association with accelerated adventitial angiogenesis. The alginate vehicle alone appeared to promote graft failure and is therefore not the optimal vehicle for stem cell delivery to vein grafts.