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Alloimmunity to Human Endothelial Cells Derived from Cord Blood Progenitors¹

Department of Immunobiology, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06520

There is considerable interest in exploiting circulating endothelial progenitor cells (EPCs) for therapeutic organ repair. Such cells may be differentiated into endothelial cells (ECs) in vitro and then expanded for use in tissue engineering. Vessel-derived ECs are variably immunogenic, depending upon tissue source, and it is unknown whether ECs derived from cord blood EPCs are able to initiate an allogeneic response. In this study, we compare the phenotype and alloantigenicity of human cord blood progenitor cell-derived ECs with HUVECs isolated from the same donors. Human cord blood progenitor cell-derived ECs are very similar to HUVECs in the expression of proteins relevant for alloimmunity, including MHC molecules, costimulators, adhesion molecules, cytokines, chemokines, and IDO, and in their ability to initiate allogeneic CD4⁺ and CD8⁺ memory T cell responses in vitro and in vivo. These findings have significant implications for the use of cord blood EPCs in regenerative medicine or tissue engineering.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institute of Health Grants HL-51015, HL85416, and HL-70295 and Programme 3+3 Fellowship from the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain (to Y.S.).

² Address correspondence and reprint requests to Dr. Jordan S. Pober, Yale University School of Medicine, 10 Amistad Street, Room 401D, New Haven, CT 60509. E-mail address: jordan.pober{at}yale.edu

³ Abbreviations used in this paper: EC, endothelial cell; EPC, endothelial progenitor cell; HUVEC, human umbilical veins; HCBEC, human cord blood progenitor cell-derived EC; VEGF, vascular endothelial growth factor; Uea-1, Ulex europeus agglutinin 1; MFI, mean fluorescence intensity.

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