Transplantation of rat metanephroi into mice

Abstract

To determine whether transplanted metanephroi grow and differentiate after implantation into the omentum in hosts of a different species, we implanted metanephroi from embryonic day 15 (E15) rat embryos into uninephrectomized mice (hosts). Some host mice received human CTLA4Ig (hCTLA4Ig), anti-CD45RB, and anti-CD154 (tolerance-inducing agents). E15 metanephroi contained only metanephric blastema, segments of ureteric bud, and primitive nephrons with no glomeruli. Rat metanephroi did not grow or differentiate in mice that received no tolerance-inducing agents. However, by 2 wk posttransplantation in mice that received hCTLA4Ig, anti-CD45RB, and anti-CD154, metanephroi from E15 rats had enlarged, become vascularized, and formed mature tubules and glomeruli. Rat metanephroi contained cells that stained specifically for mouse CD31, a marker for sprouting endothelial cells. Some rat glomerular capillary loops stained positively for mouse CD31. Here, we show that chimeric kidneys develop from metanephroi transplanted rat-->mouse and that glomeruli are vascularized, at least in part, by host vessels.

Urine excretion strategy for stem cell-generated embryonic kidneys

“…The cloaca is expected to develop in the human, creating its own human-derived vascular system (15,16). Then we will construct a urinary excretion channel using the SWPU system.…”

Incubation of Metanephroi with Vitamin D3 Increases Numbers of Glomeruli

“…Incubation of Metanephroi with Vitamin D 3 Increases Numbers of Glomeruli Transplantations were carried out from Lewis rat embryos to adult Lewis rats. Data are presented as mean ± SEM different than control.…”

“…1 Immediately after dissection metanephroi were placed in 1 ml of a 50:50 mixture of Ham's F12:Dulbecco's modified Eagles medium at 4˚C containing 25 nM prostaglandin E1, and iron-saturated transferrin (5 ug/ml) (HF12:DMEM) for 45 minutes. [1][2][3][4] When indicated, the following additions were made to the HF12:DMEM (incubation solution): none (control); 0.01, 0. In some hosts, three weeks following transplantation, end-to-end ureteroureterostomy was performed using microvascular technique (interrupted 10-0 suture) between the ureter of a metanephros implanted in the omentum and the ureter of the kidney that had been removed.…”

“…2 Successful xenotransplantations of metanephroi have also been performed. [3][4][5] Xenotransplantation (pig into mouse) was optimal under conditions such that renal anlagen were incubated prior to implantation in a solution that contained a number of growth factors and other growth promoting agents including vitamin D 3 . 4 Vitamin D 3 , an endogenous steroid synthesized in the skin, is biologically inactive.…”

“…[3][4][5] Xenotransplantation (pig into mouse) was optimal under conditions such that renal anlagen were incubated prior to implantation in a solution that contained a number of growth factors and other growth promoting agents including vitamin D 3 . 4 Vitamin D 3 , an endogenous steroid synthesized in the skin, is biologically inactive. Formation of its major biologically active product, 1, 25-hydroxyvitamin D 3 [1,25(OH) 2 D 3 ], results from hydroxylations at position C-25 primarily in the liver and C1α primarily in the kidney.…”