Emerging evidence indicates that bone marrow derived cells (BMDC) can participate in renal repair. The current consensus finding is that donor BM derived renal epithelial cells appear at low frequency. On the other hand, there are other sources of stem cells that may contribute effectively in renal regeneration, e.g., the renal papilla is considered the niche for renal resident stem cells, metanephric mesenchyme contains embryonic renal stem cells and resident renal tubular epithelial cells can participate in tubular repair after acute injury. Based on these data, this proposal hypothesized that (a), dramatic reduction or complete ablation of podocytes will enhance BMDC becoming podocytes;(b). metanephric mesenchyme can participate in nephron regeneration after transplantation into recipients with acute glomerular injury and (c). renal resident cells may participate in podocyte regeneration. The long-term objective of this proposal and beyond is to optimize conditions to improve podocyte repair/regeneration by stem cells to prevent or attenuate the progression of acute or chronic glomerular disease into end stage renal disease (ESRD). The immediate goal of this proposed work is to establish new mouse models with inducible, modifiable glomerular injuries to serve as model system to study plasticity of stem cells, compare the efficiency and capacity of different sources of (stem) cells in renal repair. The proposed project will shed fresh lights on the robustness of plasticity of different stem cells in renal repair under proposed experimental settings. The findings of this project will help to further understand the underlying cellular and molecular mechanism of glomerular repair and to pave the way for stem cell based therapy for various glomerular diseases that progress inevitablly toward end stage renal failure without a sound cure.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Guo, Jian-Kan; Shi, Hongmei; Koraishy, Farrukh et al. (2013) The Terminator mouse is a diphtheria toxin-receptor knock-in mouse strain for rapid and efficient enrichment of desired cell lineages. Kidney Int 84:1041-6
Weiss, Robert M; Guo, Songshan; Shan, Alan et al. (2013) Brg1 determines urothelial cell fate during ureter development. J Am Soc Nephrol 24:618-26
Guo, Jian-Kan; Marlier, Arnaud; Shi, Hongmei et al. (2012) Increased tubular proliferation as an adaptive response to glomerular albuminuria. J Am Soc Nephrol 23:429-37
Liu, Na; Guo, Jian-Kan; Pang, Maoyin et al. (2012) Genetic or pharmacologic blockade of EGFR inhibits renal fibrosis. J Am Soc Nephrol 23:854-67
Guo, Jian-Kan; Cantley, Lloyd G (2010) Cellular maintenance and repair of the kidney. Annu Rev Physiol 72:357-76