Vascular smooth muscle cells of recipient origin mediate intimal expansionafter aortic allotransplantation in mice

Intimal expansion by vascular smooth muscle cells (SMCs) is a characteristi c feature of graft vascular disease. Whether graft intimal SMCs arise from donor or recipient tissue is not well established but has important pathoge netic implications. We examined for the presence of male cells in the expan ded intima of sex-mismatched mouse aortic allografts (C57BL/6-to-BALB/c) at 30 or 60 days after transplant by in situ hybridization using a Y-chromoso me probe. Study groups included male-to-female allografts, female-to-male a llografts, and female-to-female allografts in recipients previously engraft ed with male bone marrow. Although intimal expansion developed in all allog rafts, male-to-female allografts lacked Y-chromosome-positive intimal cells . In contrast, such cells were abundant in female-to-male allografts and mo st of these cells co-labeled for smooth muscle cr-actin by immunostain. Fem ale-to-female allografts in recipients with male bone marrow showed a limit ed number of intimal Y-chromosome-positive cells. However, none of these cl early co-labeled for smooth muscle a-actin and their numbers declined throu ghout time, consistent with graft-infiltrating inflammatory cells. We concl ude that intimal expansion of mouse aortic allografts is mediated by SMCs t hat originated from the recipient. There was little evidence of their deriv ation from the bone marrow, suggesting instead the adjacent host aorta as t he primary source of intimal SMCs.