In studies that provide the background for this application we have transplanted rat metanephric allografts and xenografts into adult rodent hosts. We have established that: 1) metanephroi can be transplanted into the omentum of outbred or inbred rats without the use of immune suppression such that they undergo growth and differentiation in hosts, acquire a blood supply from the host, and clear inulin from the host's circulation; 2) metanephroi can be transplanted across the rat MHC and this is possible because of a state of peripheral tolerance due to T cell ignorance; 3) metanephroi can be stored in vitro for at least 3 days prior to transplantation without affecting growth, development and function in hosts; 4) xenotransplantation of metanephroi across a concordant barrier (rat to mouse) can be performed; and 5) inulin clearances of transplanted metanephroi (rat to rat) can be increased, using growth factors, by a factor of 225 relative to clearances obtained in the original group of transplants. The overall unifying hypothesis to be tested by studies outlined in this competitive renewal application is that renal fnction sufficient to sustain life can result from allograft metanephroi transplanted into the abdominal cavity of adult rats after native kidneys are removed. To this end, the Principal Investigator proposes to carry out a series of investigations the specific aim of which is to determine whether growth factors and renal growth promoting agents can enhance the development growth and function of transplanted allograft metanephroi such that such one or two transplanted developed metanephroi can sustain life in a rat after native kidneys are removed. Our studies will provide insight into the physiology and feasibility of a novel means of renal transplantation that could be applied to humans.
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