Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice
Marina Burgos-Silva1,2, Patricia Semedo-Kuriki1, Cassiano Donizetti-Oliveira1
1Nephrology Division, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Abstract:
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.
Insights
Adipose tissue-derived stem cells (AdSCs) protect kidneys from injury by regulating inflammation and cell cycle. This treatment reduces acute kidney injury and chronic kidney fibrosis, improving overall kidney function.
Area of Science:
- Nephrology
- Regenerative Medicine
- Immunology
Background:
- Acute and chronic kidney injuries (AKI and CKI) are major causes of renal failure with high mortality.
- Current therapies for kidney injury are limited, driving research into stem cell applications.
- Mesenchymal stem cells (MSCs) show promise, but their mechanisms require further elucidation.
Purpose of the Study:
- To investigate the therapeutic potential of adipose tissue-derived stem cells (AdSCs) in a mouse model of folic acid-induced nephrotoxicity.
- To understand the mechanisms underlying AdSC-mediated kidney protection, focusing on inflammation and cell cycle regulation.
Main Methods:
- Induction of nephrotoxicity using folic acid (FA) in FVB mice.
- Administration of AdSCs post-FA induction.
- Assessment of kidney function (serum urea), inflammatory markers (chemokines, neutrophil infiltrate), fibrosis (collagen deposition), and cytokine expression at 24 hours and 4 weeks post-treatment.
Main Results:
- AdSC treatment significantly improved kidney function within 24 hours, indicated by reduced serum urea.
- Treatment modulated immune response by decreasing chemokine expression and neutrophil infiltration.
- Long-term analysis (4 weeks) revealed reduced kidney fibrosis and chronic inflammation, evidenced by decreased collagen deposition and tissue chemokine/cytokine levels.
Conclusions:
- AdSC treatment confers a protective effect against nephrotoxic kidney injury.
- The protective mechanisms involve modulating inflammation and regulating the cell cycle.
- AdSCs reduce kidney damage, improve function, inhibit fibrosis, and provide long-term immune regulation.
