Transplantation of pig metanephroi

Abstract

To determine whether pig metanephroi grow and differentiate after allotransplantation or xenotransplantation across a highly disparate barrier, we implanted metanephroi from embryonic day 28 (E28) pig embryos into the omentum of unilaterally nephrectomized adult pigs or C57Bl/6J mice (hosts). Some mouse hosts received anti-CD45RB, anti-CD154, and anti-CD11a (costimulatory blockade). E28 pig metanephroi were < 0.2 mm in diameter and contained only metanephric blastema and segments of ureteric bud. Pig metanephroi transplanted into pigs underwent growth and differentiation of nephrons over a 2 week period without the need for costimulatory blockade of hosts. In contrast, pig metanephroi did not grow or differentiate in mice that received no costimulatory blockade. However, by 2 weeks posttransplantation in mice in which costimulation was blocked, metanephroi from E28 pigs had enlarged, become vascularized, and had formed mature tubules and glomeruli. By 3 weeks posttransplantation in mice, metanephroi had grown to the point that they were approximately half the volume of the native mouse kidney. Here we show that growth and development of pig metanephroi occurs posttransplantation across an allogeneic or highly disparate xenogeneic barrier.