Stem cells in renal biology: bone marrow transplantation for the treatment of IgA nephropathy.
The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated whether the fundamental pathogenesis of IgAN lies in bone marrow stem cells (BMCs) and whether bone marrow transplantation from normal C57BL/6j (B6) mice can attenuate glomerular lesions in a murine IgAN model (high serum level IgA ddY mouse; HIGA mouse). Mesangial deposits of IgA and C3 and glomerular sclerosis in HIGA recipients of BMCs from B6 mice (B6-->HIGA) were decreased as compared with those in HIGA recipients of BMCs from HIGA mice (HIGA-->HIGA). Furthermore, the serum levels of IgA and macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. Of note, bone marrow derived H-2(b)-positive cells from B6 donors were observed in the glomeruli of H-2(b)-negative HIGA recipients. Our data suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells and that bone marrow transplantation from normal mice may not only replace recipients' immune cells with donors' BMCs, but also regenerate glomerular cells in HIGA mice. This approach offers a promising strategy for the treatment of IgAN.
Imasawa
Toshiyuki
T
Department of Internal Medicine, Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, Japan. imasawa@nifty.com
Utsunomiya
Yasunori
Y
D000367:Age Factors; D000818:Animals; D016026:Bone Marrow Transplantation; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006183:H-2 Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007070:Immunoglobulin A / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D006183:H-2 Antigens; D007070:Immunoglobulin A