Engraftment of a vascularized human skin equivalent

Abstract

Clinical performance of currently avail able human skin equivalents is limited by failure to develop perfusion. To address this problem we have developed a method of endothelial cell transplantation that promotes vascularization of human skin equiva lents in vivo. Enhancement of vascularization by Bcl‐2 overexpression was demonstrated by seeding human acellular dermis grafts with human umbilical vein en dothelial cells (HUVEC) transduced with the survival gene Bcl‐2 or an EGFP control transgene, and subcuta neous implantation in immunodeficient mice ( n =18). After 1 month the grafts with Bcl‐2‐transduced cells contained a significantly greater density of perfused HUVEC‐lined microvessels (55.0/mm 3 ) than controls (25.4/mm 3 , P =0.026). Vascularized skin equivalents were then constructed by sequentially seeding the api cal and basal surfaces of acellular dermis with cultured human keratinocytes and Bcl‐2‐transduced HUVEC, respectively. Two weeks after orthotopic implantation onto mice, 75% of grafts ( n =16) displayed both a differentiated human epidermis and perfusion through HUVEC‐lined microvessels. These vessels, which showed evidence of progressive maturation, acceler ated the rate of graft vascularization. Successful trans plantation of such vascularized human skin equivalents should enhance clinical utility, especially in recipients with impaired angiogenesis.—Schechner, J. S., Crane, S. K., Wang, F., Szeglin, A. M., Tellides, G., Lorber, M. I., Bothwell, A. L. M., Pober, J. S. Engraftment of a vascularized human skin equivalent. FASEB J. 17, 2250‐2256 (2003)