Published online Sep 26, 2022. doi: 10.4252/wjsc.v14.i9.729
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
Processing time: 123 Days and 8.3 Hours
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).
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.
To investigate the mechanisms of mitochondrial transfer between MSC and high glucose-injured GECs or streptozotocin (STZ)-induced DKD rats.
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.
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.
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.
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.