Abstract: SA-PO428
Amniotic Fluid Stem Cells Ameliorate Experimental Acute Renal Failure via Induction of Autophagy and Inhibition of Apoptosis
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Minocha, Ekta, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
- Sinha, Rohit Anthony, Sanjay Gandhi Insitute of Medical Sciences, Lucknow, Uttar Pradesh, India
- Jain, Manali, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
- Chaturvedi, Chandra Prakash, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
- Nityanand, Soniya, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Background
Amniotic fluid stem cells (AFSC) have been shown to contribute in renal repair after Acute Renal Failure (ARF), however, the mechanism responsible for its renoprotective effects still remains unclear. Therefore, in the present study we evaluated the therapeutic efficacy of AFSC and investigated the underlying mechanisms responsible for its renoprotective effect.
Methods
To study the therapeutic potential of AFSC, ARF was induced in rats by a single dose of cisplatin. Five days after cisplatin injection, AFSC or normal saline were injected intravenously. On day 3 and 7 post-therapy, blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Furthermore, to confirm whether the protective effects of AFSC on cisplatin-induced apoptosis are dependent on autophagy, chloroquine, an autophagy inhibitor, was administered intra-peritoneally.
Results
Administration of AFSC in rats with ARF, resulted in improvement of renal function and attenuation of renal damage as reflected by decreased blood urea nitrogen and serum creatinine levels and alleviation in tubular cell apoptosis as assessed by lower Bax/Bcl2 ratio and decreased levels of pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group there was increased activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further aggravated the deterioration in renal structure and function caused by cisplatin.
Conclusion
This study suggests that induction of autophagy is essential for the renoprotective effects of AFSC against cisplatin-induced apoptosis. Collectively, our results show that AFSC ameliorate cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis.
Funding
- Government Support - Non-U.S.