Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2024; 16(5): 525-537
Published online May 26, 2024. doi: 10.4252/wjsc.v16.i5.525
Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury: A comparative analysis with mesenchymal stem cells
Fang Li, Bin Zhao, Lei Zhang, Guo-Qing Chen, Li Zhu, Xiao-Ling Feng, Meng-Jia Gong, Cheng-Chen Hu, Yuan-Yuan Zhang, Ming Li, Yong-Qiang Liu
Fang Li, Bin Zhao, Lei Zhang, Guo-Qing Chen, Li Zhu, Xiao-Ling Feng, Yong-Qiang Liu, Department of General Surgery, Chongqing General Hospital, Chongqing 401147, China
Meng-Jia Gong, Cheng-Chen Hu, Yuan-Yuan Zhang, Ming Li, Department of Pediatric Research Institute, Children’s Hospital of Chongqing Medical University, Chongqing 401147, China
Co-first authors: Fang Li and Bin Zhao.
Author contributions: Zhang YY and Li M conceptualised the study; Zhang YY and Liu YQ designed the study; Li F and Zhao B performed the experiments; Chen GQ and Zhu L prepared the figures; Zhu L and Liu YQ acquired funding; Li F and Gong MJ managed the study; Gong MJ and Zhang YY supervised the study; Feng XL and Hu CC drafted the manuscript; Li F, Zhao B, Zhang L, Chen GQ, Zhu L, Feng XL, Gong MJ, Hu CC, Zhang YY, Li M, and Liu YQ reviewed and edited the manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the local ethics review committee. All participants provided written informed consent prior to research participation.
Institutional animal care and use committee statement: Animal experiments were executed under the policies of the Laboratory Animal Ethical Commission of Chongqing Medical University. This protocol was approved by the Institutional Review Board of Chongqing Medical University and performed in accordance with the ethical standards prescribed by the Helsinki Declaration of the World Medical Association.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data supporting the findings of this study are available upon reasonable request from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Qiang Liu, MD, PhD, Assistant Professor, Department of General Surgery, Chongqing General Hospital, No. 118 Xingguang Avenue, Liangjiang New District, Chongqing 401147, China. wklyq007@163.com
Received: December 19, 2023
Revised: February 5, 2024
Accepted: April 7, 2024
Published online: May 26, 2024
Processing time: 156 Days and 15.4 Hours
Abstract
BACKGROUND

Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.

AIM

To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI.

METHODS

Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered via tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs).

RESULTS

Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation.

CONCLUSION

Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.

Keywords: Urine-derived stem cells; Regenerative medicine; Acute kidney injury; Renal function recovery; Cell therapy

Core tip: This study reveals that urine-derived stem cells (USCs) significantly enhance renal function and histological recovery in severe combined immune deficiency mice with glycerol-induced acute kidney injury (AKI). By comparing USCs with bone marrow-derived mesenchymal stem cells, the research highlights USCs’ potential as a novel, non-invasive cell source for AKI treatment. The findings suggest that USCs, through their multidifferentiation potential and secretion of various cytokines and growth factors, offer a promising therapeutic strategy for AKI, potentially altering clinical approaches to renal repair.