title: Adipose-derived stem cells improve renal function in a mouse model of IgA nephropathy.
abstract: T-cell dysregulation plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Adipose-derived stem cells (ASCs) have been reported to be able to prevent tissue damage through immune-modulating effects. To evaluate the effects of ASCs in high IgA ddY (HIGA) mice, ASCs were isolated from HIGA mice with different stages of IgAN before and after disease onset. ASCs were injected at a dose of 5×10(6) cells/kg body weight through the tail vein every 2 weeks for 3 months. Although the administered ASCs were rarely detected in the glomeruli, 24-h proteinuria was markedly decreased in all ASC-treated groups. Although glomerular deposition of IgA was not significantly different among groups, mesangial proliferation and glomerulosclerosis were dramatically decreased in most ASC treatment groups. In addition, levels of fibrotic and inflammatory molecules were markedly decreased by ASC treatment. Interestingly, ASC therapy significantly decreased Th1 cytokine activity in the kidney and caused a shift to Th2 responses in spleen T-cells as determined by FACS analysis. Furthermore, conditioned media from ASCs abrogated aggregated IgA-induced Th1 cytokine production in cultured HIGA mesangial cells. These results suggest that the beneficial effects of ASC treatment in IgAN occur via paracrine mechanisms that modulate the Th1/Th2 cytokine balance. ASCs are therefore a promising new therapeutic agent for the treatment of IgAN.
authors.affiliation: Department of Internal Medicine, Korea University Ansan Hospital, Ansan, South Korea.
authors.forename: Young Youl
authors.initials: YY
authors.lastname: Hyun
authors.forename: In Ok
authors.initials: IO
authors.lastname: Kim
authors.forename: Mi Hyung
authors.initials: MH
authors.lastname: Kim
authors.forename: Deok Hwa
authors.initials: DH
authors.lastname: Nam
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Song
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Cha
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Hyun Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Han
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000628:therapy*; D007678:Kidney Glomerulus / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism