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Renal Progenitors On Extracellular Matrix As A Potential Tool for Kidney Regeneration

Saturday, October 20, 2012
Grand Ballroom A/B (Hilton Riverside)
Ilenia Zanusso, PhD1, Stefano Da Sacco, PhD1, Scott Leslie, MD2, Astgik Petrosyan, BS1, Kevin Lemley, MD/PhD3, Maria Teresa Conconi, PhD1, Laura Perin, PhD1 and Roger E. De Filippo, MD1, (1)Pediatric Urology, Children's Hospital Los Angeles, Los Angeles, CA, (2)Urology, USC Institute of Urology, Keck School of Medicine, Los Angeles, CA, (3)Nephrology, Children's Hospital Los Angeles, Los Angeles, CA

Purpose Congenital abnormalities of the kidney and urinary tract (CAKUT) still remains a significant contributing factor for chronic kidney disease and end organ failure. Current treatments are directed towards slowing progression before dialysis and/or transplantation become necessary. The scarcity of allografts, cost, and side effects have prompted efforts at investigating new tools for kidney regeneration. Tissue engineering that combines a natural or biodegradable scaffold with cells and growth factors could be a new approach to discover an alternative tool for replacing significantly impaired or non-functional kidney tissue. Our laboratory has previously reported that human amniotic fluid (AF) presents a new source of renal progenitor cells. 

Methods A subpopulation of renal progenitor cells expressing CD24 and OB-cadherin were isolated from AF.  Using a detergent-enzymatic method we produced mouse decellularized whole kidney extracellular matrix (ECM).  Mouse kidney ECM was seeded with renal progenitor cells, implanted into the kidney of nude mice, and harvested at one month to look for structure and phenotypic expression.  

Results One month after surgery, implanted ECM in situ showed invasion of vessels (angiogenesis) and renal tubular-like structures. In addition to seeded scaffolds configuring into 3D renal structures, cells positive for markers associated with several essential renal cell types, such as mesangial, podocytes and tubular cells were detected.   

Conclusion These results suggest that renal progenitor cells from AF seeded into renal ECM could represent  a unique investigational approach for kidney regeneration that may be used to augment or replace damaged or compromised kidney tissue from either congenital or chronic disease.