Human Endothelial Progenitor Cell-Seeded Hybrid Graft: Proliferative and Antithrombogenic Potentials in Vitro and Fabrication Processing

Abstract

In this article, we show that human endothelial progenitor cells (EPCs) in circulating peripheral blood may be a novel cell source for a cell-incorporated engineered vascular graft. Cultures of human peripheral blood mononuclear cells collected by the density gradient technique developed highly proliferative EPC colonies, which expanded with culture time. The production rates of antiplatelet substances such as endothelial-type nitric oxide synthase and 6-keto-prostaglandin-F₁-α were approximately one-third and approximately one-half of those of mature endothelial cells (ECs), respectively. On the other hand, the tissue-type plasminogen activator production rate of EPCs was almost the same as that of ECs. EPCs were seeded and cultured on a small-diameter compliant graft (inner diameter, 1.5 mm) made of microporous segmented polyurethane film coated with a photo-reactive gelatin layer, and subsequently subjected to hydrodynamic shear stress by ex vivo circulation. EPCs fully covering the graft elongated and aligned themselves with the direction of the flow, resulting in the production of an integrated EPC-engineered graft. These results indicate that EPCs, which have high proliferative potential and high antithrombogenic potential, comparable to those of ECs, are a suitable cell source for cardiovascular tissue engineering.