Creation of a functioning chimeric mammalian kidney

Abstract

The possibility of adding new nephrons to the mammalian kidney was studied. Embryonic metanephric tissue was implanted into the renal cortex of neonatal mice less than 24 hours old, and the development of the chimeric kidney was followed over the following two to four weeks. Donor tissue was obtained from the homozygous beige mouse and a mouse line transgenic for the β-globin gene, which provided distinct cellular and nuclear markers which were used to distinguish donor from recipient nephrons. Differentiation and growth of donor nephrons occurred in the host kidney and included vascularized glomeruli, mature proximal tubules, and tubular extensions into the renal medulla. Glomerular filtration was demonstrable in donor nephrons using FITC-dextran as a marker of filtration into the proximal tubules. Transplantation of metanephric tissue into adult mouse kidneys did not lead to glomerular or tubular differentiation. This study demonstrates the feasibility of adding functioning nephrons to mammalian kidneys in species in which there is ongoing nephrogenesis post-natally.