Abstract
AbstractInjury to podocytes is a principle cause of initiation and progression of both immune and non-immune mediated glomerular diseases that result in proteinuria and decreased function of the kidney. Current advances in regenerative medicine shed light on the therapeutic potential of cell-based strategies for treatment of such disorders. Thus, there is hope that generation and transplantation of podocytes from induced pluripotent stem cells (iPSCs), could potentially be used as a curative treatment for glomerulonephritis caused by podocytes injury and loss. Despite several reports on the generation of iPSC-derived podocytes, there are rare reports about successful use of these cells in animal models. In this study, we first generated a model of anti-podocyte antibody-induced heavy proteinuria that resembled human membranous nephropathy and was characterized by the presence of sub-epithelial immune deposits and podocytes loss. Thereafter, we showed that transplantation of functional iPSC-derived podocytes following podocytes depletion results in recruitment of iPSC-derived podocytes within the damaged glomerulus, and leads to attenuation of proteinuria and histological alterations. These results provided evidence that application of iPSCs-derived renal cells could be a possible therapeutic strategy to favorably influence glomerular diseases outcomes.
Publisher
Springer Science and Business Media LLC
Reference66 articles.
1. Lai, W. L. et al. Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment. J. Formos. Med. Assoc. 114, 102–111 (2015).
2. Asanuma, K. & Mundel, P. The role of podocytes in glomerular pathobiology. Clin. Exp. Nephrol. 7, 255–259, https://doi.org/10.1007/s10157-003-0259-6 (2003).
3. Meliambro, K., He, J. C. & Campbell, K. N. The podocyte as a therapeutic target in proteinuric kidney disease. Journal of Nephrology & Therapeutics 2013 (2013).
4. Martin, C. E. & Jones, N. Nephrin signaling in the podocyte: an updated view of signal regulation at the slit diaphragm and beyond. Front. Endocrinol. (Lausanne) 9, 302 (2018).
5. Luo, W. et al. Alternative pathway is essential for glomerular complement activation and proteinuria in a mouse model of membranous nephropathy. Front. Immunol. 9, 1433 (2018).
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献