Human Endometrial Stromal/Stem Cells Inhibit Apoptosis in Cisplatin-Induced Acute Kidney Injury in Male Wistar Rats

Hadis Zeinali; Mahnaz Azarnia; Peyman Keyhanvar; Reza Moghadasali; Somayeh Ebrahimi-Barough

doi:10.22074/cellj.2021.7322

Human Endometrial Stromal/Stem Cells Inhibit Apoptosis in Cisplatin-Induced Acute Kidney Injury in Male Wistar Rats

Cell J. 2021 Oct;23(5):568-575. doi: 10.22074/cellj.2021.7322. Epub 2021 Oct 30.

Authors

Hadis Zeinali¹, Mahnaz Azarnia², Peyman Keyhanvar^{3

4}, Reza Moghadasali⁵, Somayeh Ebrahimi-Barough⁶

Affiliations

¹ Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
² Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. Email: azarnia@khu.ac.ir.
³ Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Department of Medical Nanotechnology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
⁵ Department of Stem Cells and Developmental Biology, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
⁶ Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Objective: Acute kidney injury (AKI) is referred to as sudden decline in the function of kidney. Human endometrial stromal/stem cells (hEnSCs) are mesenchymal stem cell (MSC)-like cells, which are suitable candidates for regenerative medicine purposes, yet the effect of hEnSCs on cisplatin-induced AKI has not been studied; therefore, the present study was conducted to investigate this gap in the literature.

Materials and methods: In this experimental study, hEnSCs were obtained from endometrial biopsy using collagenase I and were then cultured in DMEM/F12 medium. A total of 48 male Wistar rats (150-200 g) were classified into four groups: intact -receiving no treatment, model -receiving 5 mg/kg of body weight cisplatin, as well as phosphate-buffered saline (PBS) and cell -receiving either PBS or hEnSCs for three hours after cisplatin injection, respectively. Biochemical parameters, pathologic scores, apoptosis assay, Bcl-2 and Tnf-α expression were evaluated on day 5.

Results: On day 5 post-transplantation we observed that HEnSCs injection has led to a decrease in both blood urea nitrogen (BUN) and serum creatinine (SCr), compared to the model and PBS groups (0.82 ± 0.03 vs. 1.42 ± 0.06, 1.09 ± 0.05 mg/dl and 61.53 ± 3.07 vs. 116.60 ± 2.12, 112.00 ± 1.35 mg/dl, respectively). The highest levels of pathologic scores were observed in model and PBS groups, while hEnSCs transplantation resulted in a decrease in pathologic scores (149.10 ± 7.03, 141.50 ± 4.68 vs. 118 ± 2.16). HEnSCs significantly decreased the percentage of TUNELpositive cells in the cell group compared with model and PBS groups (20.37 ±. 3.37 vs. 33.67 ± 1.79, 31.53 ± 1.05 in glomeruli and 15.10 ± 1.47 vs. 42.33 ± 1.72, 39.23 ± 1.61 in tubules). In addition, HEnSCs resulted in upregulation of Bcl-2 and downregulation of Tnf-α in the cisplatin-induced AKI.

Conclusion: Our results showed that injection of hEnSCs may improve AKI through lowering the amount of apoptosis in renal cells.

Keywords: Acute Kidney Injury; Apoptosis; Cisplatin; Human Endometrial Stromal/Stem Cell.