Differential origin for endothelial and mesangial cells after transplantation of pig fetal renal primordia into rats

Xenotransplantation of renal primordia in lieu of human kidney allografts has been proposed as a solution for the lack of organ availability. We and others have shown that growth and development of pig renal primordia occur post-transplantation across a highly disparate xenogenic barrier to rat. The origins (donor versus host) of endothelial cells (ECs) and mesangial cells (MCs) in grafts are incompletely delineated. In the present study, we investigated using immunohistochemistry, the origin ECs and MCs of the metanephric xenografts originating from embryonic day 28 (E28) pig embryos transplanted into rats. We employed species-specific antibodies: anti-rat endothelial cell antigen-1 (RECA-1) and -CD31 to detect rat- and pig-derived ECs, respectively; and anti-Thy-1 and -vimentin to detect rat- and pig-derived MCs, respectively. Both intra- and extraglomerular ECs in the xenografts were stained exclusively with rat-specific anti-RECA-1 at 5, 7, or 8 weeks post-transplantation, whereas ECs were not stained with pig-specific anti-CD31. In contrast, MCs in the xenografts were stained predominantly using the pig specific anti-vimentin, although a few glomeruli were positive for rat-specific anti-Thy-1. We conclude that the predominant origin of ECs post-transplantation of embryonic pig metanephroi into rats is the host, whereas MCs originate mainly from the donor.