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Open Access Adipose-Derived Stem Cells Improve Renal Function in a Mouse Model of IgA Nephropathy

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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 5×106 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.

Keywords: Adipose-derived stem cells (ASCs); Glomerulosclerosis; HIGA mice; Proteinuria; Th1 cytokine

Document Type: Research Article


Publication date: November 1, 2012

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

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