Translational Nephrology Bone marrow transplantation rescues Alport mice*

In the 9 May 2006 issue of Proc Natl Acad Sci USA, Sugimoto and colleagues [1] described fascinating data on a potential approach to treat Alport’s syndrome, a rare genetic disease leading to renal failure, which so far could not be cured. The work was highly publicized and discussed in both scientific journals and the lay press. Alport’s syndrome derives from a mutation of either the a3, a4 or a5 chain of type IV collagen, i.e. collagen types that constitute basement membranes in the renal glomerulus, the ear and the eye. Mice that are genetically deficient of the a3(IV)-chain (‘Alport mice’) develop a renal phenotype very similar to that of Alport patients (Figure 1), i.e. proteinuria, glomerulonephritis and subsequent tubulointerstitial fibrosis starting at 8 weeks of age and leading to death due to renal failure at 20–23 weeks. In the study by Sugimoto et al. [1], 8 week-old Alport mice were lethally irradiated and then received an allogenic unfractionated bone marrow transplant from either LacZ mice, i.e. mice with a normal collagen production plus expression of the LacZ marker in all cells, or from another Alport mouse. Whereas the latter had no effect on the phenotype, the allogenic bone marrow led to markedly reduced proteinuria upon follow-up, and improved renal function as well as renal histology. LacZ-positive cells constituted about 10% of the glomerular cells and were found in podocyte and mesangial cell locations. The glomerular staining pattern for the a3and a5(IV) chains was partially restored. If these data can be confirmed and extended by showing that the treatment delays death from renal failure in Alport mice (see subsequently), there would be several major implications of this study.