Human Umbilical Cord Blood–Derived Endothelial Cells Reendothelialize Vein Grafts and Prevent Thrombosis

Abstract

Objective-To accelerate vein graft reendothelialization and reduce vein graft thrombosis by infusing human umbilical cord blood-derived endothelial cells (hCB-ECs) because loss of endothelium contributes to vein graft thrombosis and neointimal hyperplasia. Methods and Results-Under steady flow conditions in vitro, hCB-ECs adhered to smooth muscle cells 2.5 to 13 times more than ECs derived from peripheral blood or human aorta (PϽ0.05). Compared with peripheral blood and human aorta ECs, hCB-ECs had 1.4-fold more cell surface ␣ 5 ␤ 1 integrin heterodimers per cell (PϽ0.05) and proliferated on fibronectin 4-to 10-fold more rapidly (PϽ0.05). Therefore, we used hCB-ECs to enhance reendothelialization of carotid interposition vein grafts implanted in NOD.CB17-Prkdc scid /J mice. Two weeks postoperatively, vein grafts from hCB-EC-treated mice demonstrated approximately 55% reendothelialization and no luminal thrombosis. In contrast, vein grafts from sham-treated mice demonstrated luminal thrombosis in 75% of specimens (PϽ0.05) and only approximately 14% reendothelialization. In vein grafts from hCB-EC-treated mice, 33Ϯ10% of the endothelium was of human origin, as judged by human major histocompatibility class I expression. Key Words: endothelial function Ⅲ thrombosis Ⅲ vascular biology Ⅲ vascular surgery Ⅲ integrin S aphenous vein graft failure from thrombosis occurs with remarkable frequency: approximately 3% to 12% within the first postoperative month 1 and 28% within the first postoperative year. 2 Vein graft thrombosis is generally attributed to alterations in the vessel wall and flow dynamics, vein graft endothelial damage associated with both vein harvest and vein graft distension by arterial pressure, and consequent compromise of anticoagulant vessel properties. 1 Among these factors, the most practical target for therapy appears to be maintenance or restoration of the vein graft endothelium. Conclusion-TheReendothelialization of vein grafts is a relatively slow process that involves proliferation and migration of both graft-intrinsic endothelial cells (ECs) and graft-extrinsic ECs, 3 which may derive from adjacent arterial endothelium or circulating endothelial progenitor cells (EPCs). 4,5 Consequently, accelerating EC growth or increasing EC number with exogenous ECs may accelerate vein graft reendothelialization. Exogenous ECs derived from peripheral and umbilical cord blood EPCs are relatively easy to obtain and possess substantial replicative capacity. 6 Most studies that have examined adhesion of ECs to damaged vasculature have used ECs obtained from earlyoutgrowth cultures of EPCs, which are of a myeloid lineage and do not exhibit the antithrombotic properties of ECs. [7][8][9] Few vascular repair experiments have examined ECs derived from late-outgrowth cultures of EPCs isolated from adult or umbilical cord blood. These late-outgrowth EPCs, or endothelial colony-forming cells, exhibit characteristics only of ECs and not of monocytes. 10,11 ECs obtained from lateoutgrowth cultures of peripheral blood...

Comparison of Mixed and Lamellar Coculture Spatial Arrangements for Tissue Engineering Capillary NetworksIn Vitro

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Vein graft neointimal hyperplasia is exacerbated by CXCR4 signaling in vein graft-extrinsic cells

“…Consequent to the barotrauma associated with implantation in the arterial circuit, 3, 24, 28 defects in the vein graft endothelium trigger platelet adhesion to the vein graft’s luminal surface; platelet-secreted SDF-1 29 then functions to recruit vein graft-extrinsic cells to the vein graft. During vein graft arterialization, cells of the burgeoning vein graft media and neointima also secrete SDF-1—as Fig 2 demonstrates.…”

In vitro 3D angiogenesis assay in egg white matrix: comparison to Matrigel, compatibility to various species, and suitability for drug testing

“…In the case of endothelial and mural cell coculture, vascular smooth muscle cells (VSMCs) secrete basement membrane proteins that enable adhesion of endothelial cells (ECs). [1][2][3][4] In addition, proangiogenic factors released by VSMCs promote development and stabilization of capillaries. VSMCs and ECs grow in a three-dimensional (3D) multilayered structure similar to vascular wall structure.…”