Renal stem cells: possible role in kidney patholog.. (RESCARF)
Renal stem cells: possible role in kidney pathologies and as new theraputic tools
Start date: Oct 1, 2008,
End date: Sep 30, 2012
Chronic Kidney Disease (CKD) affects 11% of the adult population and is considered by the WHO as one of the health emergencies of the 21st century. Although cell therapy might be beneficial for CKD, human stem cells that might be used to improve kidney function were so far unknown. Recently, we demonstrated the existence of resident stem cells in the urinary pole of the Bowman’s capsule of adult human kidney and therefore named as adult parietal epithelial multipotent progenitors (APEMP). Injection of APEMP in SCID mice affected by acute renal failure, induced regeneration of tubular structures and reduced morphological and functional kidney damage. More recently, we found that APEMP are highly represented in embryonic kidneys and constitute the common progenitor of tubular cells and podocytes. The first aim of this project is to assess the regenerative properties of APEMP in in vivo models of glomerular injury and their potential use as a novel therapeutic tool to prevent the deterioration of kidney function in chronic renal failure. Second, we will try to identify the mechanisms that regulate the growth, survival, differentiation, and migration of APEMP, which is critical to set up cell therapies of renal injury which should be effective and safe. To this end, the role of different molecular pathways such as Sonic hedgehog, Wnt/beta-catenin, Notch, TGF-beta/BMP and of CXCR4, CXCR7 or CXCR3-B chemokine receptors in the regenerative activity of APEMP will be investigated. Third, to assess whether APEMP directly contribute to kidney regeneration after glomerular or tubular damage, transgenic animals in which APEMP are genetically tagged will be generated. Fourth, by using transgenic animals we will try to understand if an alteration of APEMP growth and/or differentiation is implicated in the pathogenesis of some renal disorders that frequently progress towards end stage renal disease.
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