In studies preliminary to the present proposal, we transplanted whole metanephroi from rat or mouse embryos to outbred adult Sprague Dawley rats. Some were implanted under the capsule of intact kidneys of host rats. Some were implanted intra-abdominally in host rats. The survival, vascularization and maturation of the metanephroi evident 4-10 weeks later indicate that renal organogenesis can occur under these conditions and that a chimeric kidney is the result. In contrast, transplantation of a developed (adult) kidney from one rat to another results in rejection by 7 days post-transplantation. Since transplanted metanephroi survive for weeks without immunosuppression under conditions where transplanted adult kidneys are rejected, our findings suggest that metanephric tissue is less immunogenic that adult kidney. Transplanted metanephroi clear inulin from the circulation. Inulin clearance by transplanted metanephroi is enhanced by administration of insulin-like growth factor I to hosts. The overall hypothesis to be tested in the present proposal is that renal function, sufficient to sustain life can result from metanephroi transplanted into the abdominal cavity of adult rats after native kidneys are remove. To address these questions, using the methodology employed to perform our preliminary studies, we will transplant metanephroi from rats or mice into the abdominal cavity of outbred adult rodents. They will measure inulin clearance following ureteroureterostomy, of developed functioning transplanted kidneys, to the collecting system of hosts. In addition they will study the anatomy/physiology of the transplanted metanephroi. Since transplanted metanephroi appear to be less immunogenic than adult kidneys, our studies will provide insight into the feasibility of a novel means of renal transplantation that could be applied to humans.
| Hammerman, M R (1999) Developmental nephrology comes of age. Curr Opin Nephrol Hypertens 8:7-8 |
