Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors

We found that ROP Os/+ (Os/+) mice had diffuse glomerulosclerosis and glome rular hypertrophy and that their mesangial cells (the vascular smooth muscl e cells of the glomerulus) displayed an apparent sclerosing phenotype. Sinc e mesangial cells are the major source of scar tissue in glomerulosclerosis , we postulated that the sclerosis phenotype was carried by mesangial cell progenitors and that this phenotype could be derived from the bone marrow ( BM). Therefore, we transplanted BM from Os/+ mice into congenic ROP +/+ mic e (+/+ mice), which have normal glomeruli. We found that glomeruli of +/+ r ecipients of Os/+ marrow contained the Os/+ genotype, were hypertrophied, a nd contained increased extracellular matrix. Clones of recipient glomerular mesangial cells with the donor genotype were found in all +/+ recipients t hat developed mesangial sclerosis and glomerular hypertrophy, whereas +/+ r ecipients of +/+ BM had normal glomeruli. Thus, the sclerotic (Os/+) or nor mal (+/+) genotype and phenotype were present in, and transmitted by, BM-de rived progenitors. These data show that glomerular mesangial cell progenito rs are derived from the BM and can deliver a disease phenotype to normal gl omeruli. Glomerular lesions may therefore be perpetuated or aggravated, rat her than resolved, by newly arriving progenitor cells exhibiting a disease phenotype.