Bone Marrow Transplantation Can Attenuate the Progression of Mesangial Sclerosis

¹ Yale University School of Medicine, New Haven, Connecticut
² INSERM U 636, Center for Biochemistry, Nice University, Nice, France
³ Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut

^* To whom correspondence should be addressed. E-mail: diane.krause{at}yale.edu.

	Abstract

Bone marrow (BM) transplantation has been shown to provide beneficial effects in injured organs including heart, liver and kidney. We explored the therapeutic potential of BM transplantation (BMT) in Wilms' tumor suppressor 1 (Wt1) heterozygous mice, which represent a model of mesangial sclerosis (MS). After transplantation of wildtype BM, there is statistically significantly lower urinary albumin, and increased survival in Wt1+/- recipients. Control BMT using Wt1+/- donors showed no significant beneficial effects. The longterm beneficial effect of BMT was dependent on the dose of irradiation applied to the recipients prior to BMT. At a lethal dose of 1000 cGy, the decrease in albuminuria and prolongation of lifespan in Wt1+/- mice were transient with maximal amelioration at 12 weeks, and resumption of albuminuria by 24 weeks post BMT. This was, at least in part, due to irradiation and not Wt1 heterozygosity because wildtype recipients also developed albuminuria within 24 weeks of BMT with 1000 cGy. In contrast, Wt1+/- mice transplanted after 400 cGy showed longterm improvement in albuminuria and lifespan. Approximately 0.4% of podocytes were marrow derived, a level that is unlikely to be responsible for the therapeutic effects. In addition, donor BM cells formed rings surrounding the glomeruli, and approximately one third of the cells in these rings were macrophages. In conclusion, transplantation of wildtype bone marrow attenuates progression of mesangial sclerosis in the Wt1+/- model of renal disease, and the mechanism by which this occurs may be engraftment of BM-derived cells in the renal parenchyma.