Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes

Esmail Ranjbar; Jalil Tavakol Afshari; Abolfazl KhajaviRad; Alireza Ebrahimzadeh-Bideskan; Reyhaneh Shafieian

doi:10.1515/jbcpp-2022-0159

Article

Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes

Esmail Ranjbar , Jalil Tavakol Afshari , Abolfazl KhajaviRad , Alireza Ebrahimzadeh-Bideskan and Reyhaneh Shafieian

Published/Copyright: October 10, 2022

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 34 Issue 3

Abstract

Objectives

Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI.

Methods

AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups.

Results

A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals.

Conclusions

The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

Keywords: cisplatin; conditioned medium; dental stem cell; kidney; oxidative stress

Corresponding author: Dr. Reyhaneh Shafieian, Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, VakilAbad Blv, Azadi Sq., PO 91779-48564, Mashhad, Iran; and Stem Cell and Regenerative Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran, Phone: +98 511 8002486, E-mail: shafieianr@mums.ac.ir

Funding source: Mashhad University of Medical Sciences

Award Identifier / Grant number: 981611

Research funding: This study was financially supported by Vice-Chancellor for Research, Mashhad University of Medical Sciences, Mashhad, Iran (Grant number: 981611). The present article is part of an MSc student thesis in field of anatomical sciences and cell biology at MUMS. The authors thank the technical support of Mr. MohammadAli Khodadoust and Mrs. Fatemeh Motejadded.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The research has complied with all relevant national regulations and institutional policies and has been approved by the authors’ institutional review board or equivalent committee. All the protocols of this study were approved by the Ethical Committee Acts of School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran (Ethical Code: IR.MUMS.REC.1399.477).

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Received: 2022-06-15

Accepted: 2022-09-18

Published Online: 2022-10-10

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2022-0159

Keywords for this article

cisplatin; conditioned medium; dental stem cell; kidney; oxidative stress