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

被引:108
作者
Perin, Laura [1 ,2 ]
Sedrakyan, Sargis [1 ,2 ]
Giuliani, Stefano [1 ,2 ]
Da Sacco, Stefano [1 ,2 ]
Carraro, Gianni [1 ,2 ]
Shiri, Liron [1 ,2 ]
Lemley, Kevin V. [1 ,2 ]
Rosol, Michael [1 ,2 ]
Wu, Sam [1 ,2 ]
Atala, Anthony [3 ]
Warburton, David [1 ,2 ]
De Filippo, Roger E. [1 ,2 ]
机构
[1] Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol & Regenerat Med Program, Los Angeles, CA 90027 USA
[2] Univ So Calif, Keck Sch Med, Inst Urol, Los Angeles, CA 90033 USA
[3] Wake Forest Univ, Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA
关键词
ACUTE-RENAL-FAILURE; ACUTE KIDNEY INJURY; T-CELLS; REPAIR; DIFFERENTIATION; PROLIFERATION; INFLAMMATION; PROTEIN; IL-10;
D O I
10.1371/journal.pone.0009357
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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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页数:16
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