Integration of New Embryonic Nephrons Into the Kidney

Abstract

The current report summarizes our experiments exploring the feasibility of creating a chimeric kidney, that is, an organ constituted by cells derived from more than one fertilized ovum. The overall strategy has been to obtain donor renal tissue from avian and murine embryos and to implant this into the host avian mesonephric mesoderm or into the cortex of murine neonatal kidney. In both models, donor cells were distinguished from the host by the presence of characteristic nuclear or cytoplasmic markers. Examination of quail to chick transplants showed the tandem development of mesonephric tissue in the form of bilobed organ. In the mouse chimeric kidney, examined 2 to 4 weeks postnatally, transplanted metanephric tissue grew and developed glomeruli, proximal tubules, and cords of cells, which extended into the medulla of the host kidney. Before death, intravenous FITC-dextran was administered to the host mouse. Some transplanted tubules were connected to filtering glomeruli, as judged by the presence of fluorescein within their lumens. These experimental models provide novel means with which to study nephrogenesis in vivo. Finally, if the embryonic donor tissue could be genetically engineered before implantation, the prospect of "nephron therapy" arises, in which altered implanted nephrons could deliver therapeutically useful molecules into the urine or kidney interstitium.