Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis
Related Experiment Video
Updated: Jun 15, 2026
Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Laura Perin1, Sargis Sedrakyan, Stefano Giuliani
1Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, California, United States of America.
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.
Insights
Human amniotic fluid stem cells (hAFSC) show therapeutic potential for acute tubular necrosis (ATN). These stem cells protect kidneys, reduce damage, and modulate the immune response in a mouse model of ATN.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Acute Tubular Necrosis (ATN) is a severe kidney injury damaging tubular cells and causing renal dysfunction.
- Stem-cell based therapies offer potential treatment avenues for ATN.
- Human amniotic fluid stem cells (hAFSC) have previously demonstrated potential for renal differentiation ex-vivo.
Purpose of the Study:
- To investigate the therapeutic efficacy of hAFSC in a mouse model of glycerol-induced rhabdomyolysis and ATN.
- To track the engraftment and survival of injected hAFSC in the damaged kidney.
- To evaluate the protective and immunomodulatory effects of hAFSC during the acute phase of ATN.
Main Methods:
- Induction of ATN in a mouse model using glycerol injection.
- Intra-renal administration of luciferase-labeled hAFSC.
- Bioluminescence imaging for tracking hAFSC.
- Assessment of renal function via creatinine and blood urea nitrogen (BUN) levels.
- Histological analysis of kidney tissue to evaluate tubular damage, apoptosis, and proliferation.
- Evaluation of immunomodulatory effects of hAFSC.
Main Results:
- hAFSC administration significantly reduced creatinine and BUN levels, indicating improved kidney function.
- A decrease in the number of damaged tubules and reduced apoptosis were observed in hAFSC-treated kidneys.
- Enhanced proliferation of tubular epithelial cells was noted post-hAFSC treatment.
- Bioluminescence imaging confirmed the tracking and engraftment of hAFSC in the injured kidneys.
- Significant immunomodulatory effects of hAFSC were observed throughout the ATN course.
Conclusions:
- hAFSC demonstrate successful therapeutic application in a preclinical model of ATN.
- hAFSC possess protective properties, ameliorating kidney injury by reducing cell damage and apoptosis while promoting regeneration.
- hAFSC exhibit significant immunomodulatory capacity, suggesting a role in modulating the kidney's immune environment during ATN.
- AFSC represent a promising novel stem cell source for treating renal failure associated with ATN.
