Protective Effect of Human Amniotic Fluid Stem Cells in an Immunodeficient Mouse Model of Acute Tubular Necrosis

Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2010; 5(2):e9357. DOI: 10.1371/journal.pone.0009357
Source: PubMed


Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN.

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Available from: Stefano Giuliani
    • "In addition, AFSCs exerted a pronounced anti-apoptotic action on tubular cells, whereas MSCs were less effective. In kidneys with acute tubular necrosis caused by glycerol-induced rhabdomyolysis, human AFSCs had the ability to modulate the immune response and restore physiological kidney function parameters to normal levels[16]. Similarly, when injected in an animal model of Alport syndrome , AFSCs showed the propensity to lessen inflammation and fibrosis, and restore renal function[17]. "
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    • "Human amniotic fluid stem cells, a novel class of broadly multipotent stem cells that exhibit characteristics of both embryonic and adult stem cells, have been regarded as a promising candidate for stem cell therapy [130]. Beneficial therapeutic effects of amniotic fluid stem cells have been shown in kidney injury models including acute kidney injury induced by glycerol [131, 132] or cisplatin [133], a mouse model of Alport syndrome [134], and a mouse unilateral ureteral obstruction (UUO) model [135]. "
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