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: 3.53). 02/2010; 5(2):e9357. DOI: 10.1371/journal.pone.0009357
Source: PubMed

ABSTRACT 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, Aug 19, 2015
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    • "New studies have highlighted the possibility that the same mechanism of action can be used to explain the effect of amniotic fluid stem cells in many diseases. In particular, Perin showed that in a murine model of acute tubular necrosis, the expression of inflammatory cytokines is strongly regulated after injection of AFSC (Perin et al., 2010). Down regulation of proinflammatory molecules and up-regulation of pro-regenerative and anti-flogistic cytokines resulted in a faster regeneration of the damaged tissue with higher proliferation rate, lower apoptosis and an overall better physiological profile of different renal parameters. "
    Advances in Regenerative Medicine, 11/2011; , ISBN: 978-953-307-732-1
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    • "Human AFS cells injected into an immunodeficient mouse model of the disease decreased the number of damaged tubules and reduced apoptosis. The cells also promoted the proliferation of tubular epithelial cells and appeared to have a beneficial immunomodulatory effect (Perin et al. 2010). "
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    ABSTRACT: Foetal stem cells (FSCs) can be isolated during gestation from many different tissues such as blood, liver and bone marrow as well as from a variety of extraembryonic tissues such as amniotic fluid and placenta. Strong evidence suggests that these cells differ on many biological aspects such as growth kinetics, morphology, immunophenotype, differentiation potential and engraftment capacity in vivo. Despite these differences, FSCs appear to be more primitive and have greater multi-potentiality than their adult counterparts. For example, foetal blood haemopoietic stem cells proliferate more rapidly than those found in cord blood or adult bone marrow. These features have led to FSCs being investigated for pre- and post-natal cell therapy and regenerative medicine applications. The cells have been used in pre-clinical studies to treat a wide range of diseases such as skeletal dysplasia, diaphragmatic hernia and respiratory failure, white matter damage, renal pathologies as well as cancers. Their intermediate state between adult and embryonic stem cells also makes them an ideal candidate for reprogramming to the pluripotent status.
    Journal of The Royal Society Interface 12/2010; 7 Suppl 6(Suppl 6):S689-706. DOI:10.1098/rsif.2010.0347.focus · 3.86 Impact Factor
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    Kidney international. Supplement 11/1974;
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