Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2022; 14(9): 729-743
Published online Sep 26, 2022. doi: 10.4252/wjsc.v14.i9.729
Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells
Li-Xia Tang, Bing Wei, Lu-Yao Jiang, You-You Ying, Ke Li, Tian-Xi Chen, Ruo-Fei Huang, Miao-Jun Shi, Hang Xu
Li-Xia Tang, You-You Ying, Ke Li, Ruo-Fei Huang, Department of Endocrinology, The First People’s Hospital of Yongkang Affiliated to Hangzhou Medical College, Jinhua 321300, Zhejiang Province, China
Bing Wei, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Lu-Yao Jiang, Department of Medical Rehabilitation, The First People’s Hospital of Yongkang Affiliated to Hangzhou Medical College, Jinhua 321300, Zhejiang Province, China
Tian-Xi Chen, Miao-Jun Shi, Department of Nephrology, The First People’s Hospital of Yongkang Affiliated to Hangzhou Medical College, Jinhua 321300, Zhejiang Province, China
Hang Xu, Department of Hemodialysis/Nephrology, The First People’s Hospital of Yongkang Affiliated to Hangzhou Medical College, Jinhua 321300, Zhejiang Province, China
Author contributions: Tang LX, Wei B, Li K, and Xu H designed the study; Tang LX and Wei B wrote the manuscript; Tang LX, Wei B, Jiang LY, Ying YY, Chen TX, Huang RF, and Shi MJ performed the experiments; Tang LX, Wei B, Li K, and Xu H analysed the data; and all authors have read and approved the final manuscript.
Supported by the Science and Technology Foundation of Jinhua, No. 2021-4-190.
Institutional animal care and use committee statement: The animal experiments were carried out following the National Institutes of Health Guidelines for the care and use of laboratory animals and according to protocols approved by the Animal Experimental Ethical Committee of Southeast University (Nanjing, China). The animals were acclimatized to laboratory conditions (22-25 °C, 12 h/12 h light/dark, 50% humidity, ad libitum access to food and water). All animals were euthanized by 2%-3% halothane and then carbon dioxide inhalation for kidney tissue collection.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets supporting the conclusions of this article are included within the article.
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: Hang Xu, BMed, Doctor, Occupational Physician, Department of Hemodialysis/Nephrology, The First People’s Hospital of Yongkang Affiliated to Hangzhou Medical College, No. 599, Jinshan West Road, Dongcheng District, Jinhua 321300, Zhejiang Province, China. 13758989843@163.com
Received: May 23, 2022
Peer-review started: May 23, 2022
First decision: July 6, 2022
Revised: July 18, 2022
Accepted: September 6, 2022
Article in press: September 6, 2022
Published online: September 26, 2022
ARTICLE HIGHLIGHTS
Research background

Mesenchymal stem cells (MSCs) can rescue injured target cells via mitochondrial transfer. However, little is known about how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease (DKD).

Research motivation

Mitochondria play vital roles in biological processes such as oxidative phosphorylation, cellular metabolism, and cell death. Recent studies indicate that mitochondrial damage occurs in glomerular endothelial cells (GECs) in DKD and MSCs could transfer their mitochondria to target cells. However, the mechanism of how mitochondrial transfer contributes to the high glucose-injured GECs is not well-understood.

Research objectives

To investigate the mechanisms of mitochondrial transfer between MSC and high glucose-injured GECs or streptozotocin (STZ)-induced DKD rats.

Research methods

The mitochondria of GECs and MSCs were labeled before co-cultivation. A fluorescence microscope was used to examine the mitochondrial transfer, then cell proliferation and apoptosis were detected by western blot, real-time reverse transcriptase-polymerase chain reaction, Cell Counting Kit-8, and Annexin V-FITC/PI assays. The mitochondria function [adenosine triphosphate (ATP), reactive oxygen species (ROS), and mitochondrial membrane potential] of GECs was assessed with related-detection kits. A DKD rat model was obtained by STZ administration. Renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits. In addition, histological changes were evaluated by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemical staining.

Research results

Our results demonstrated that the MitoTracker Red CMXRos labeled mitochondria were transferred from MSCs to the high glucose-injured GECs, ATP levels were increased, and the membrane potential of mitochondria was stabilized. Additionally, the transfer of mitochondria decreased pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α] and pro-apoptotic factors (caspase 3 and Bax). Transfer of healthy MSC-derived mitochondria enhanced the expression of superoxide dismutase 2, B-cell lymphoma 2, glutathione peroxidase 3, and Mitofusin 2 and inhibited ROS (mitochondrial and intracellular) and dynamin-related protein 1 expression. Notably, a transfer of healthy mitochondria from MSCs suppressed GEC apoptosis and enhanced their proliferation. Furthermore, STZ-induced DKD animal experiments showed that MSC ameliorated renal function damage and pathological progression of DKD.

Research conclusions

Our data demonstrated the existing of mitochondrial transfer in vitro, which plays a pivotal role in the rescue of GECs. Moreover, MSCs repair the renal function damage and pathological progress of DKD rats perhaps via mechanism of mitochondrial transfer.

Research perspectives

This study revealed the role and mechanism of mitochondrial transfer in the rescue of injured GECs, which can provide a scientific basis for the potential therapeutic effects of MSCs on DKD.