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Updated: May 22, 2025
Author Spotlight: Bidirectional Mitochondrial Transfer between MSCs and Retinal Pigment Epithelium Cells — Pathways and In Vivo Challenges
Published on: October 4, 2024
MSC-mediated mitochondrial transfer promotes metabolic reprograming in endothelial cells and vascular regeneration in
Jinlong Wang1,2, Shanshan Meng1, Yixuan Chen1
1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.
Background:
Mesenchymal stem cells (MSCs) are a potential therapy for acute respiratory distress syndrome (ARDS), but their mechanisms in repairing mitochondrial damage in ARDS endothelial cells remain unclear.
Methods:
We first examined MSCs' mitochondrial transfer ability and mechanisms to mouse pulmonary microvascular endothelial cells (MPMECs) in ARDS. Then, we investigated how MSC-mediated mitochondrial transfer affects the repair of endothelial damage. Finally, we elucidated the mechanisms by which MSC-mediated mitochondrial transfer promotes vascular regeneration.
Results:
Compared to mitochondrial-damaged MSCs, normal MSCs showed a significantly higher mitochondrial transfer rate to MPMECs, with increases of 41.68% in vitro (P < 0.0001) and 10.50% in vivo (P = 0.0005). Furthermore, MSC-mediated mitochondrial transfer significantly reduced reactive oxygen species (P < 0.05) and promoted proliferation (P < 0.0001) in MPMECs. Finally, MSC-mediated mitochondrial transfer significantly increased the activity of the tricarboxylic acid (TCA) cycle (MD of CS mRNA: 23.76, P = 0.032), and further enhanced fatty acid synthesis (MD of FAS mRNA: 6.67, P = 0.0001), leading to a 6.7-fold increase in vascular endothelial growth factor release from MPMECs and promoted vascular regeneration in ARDS.
Conclusion:
MSC-mediated mitochondrial transfer to MPMECs activates the TCA cycle and fatty acid synthesis, promoting endothelial proliferation and pro-angiogenic factor release, thereby enhancing vascular regeneration in ARDS.
Insights
Mesenchymal stem cells (MSCs) transfer healthy mitochondria to repair damaged endothelial cells in acute respiratory distress syndrome (ARDS). This process boosts cell growth and promotes blood vessel repair by activating key metabolic pathways.
Area of Science:
- Mitochondrial biology
- Endothelial cell function
- Regenerative medicine
Background:
- Mesenchymal stem cells (MSCs) show promise for treating acute respiratory distress syndrome (ARDS).
- The precise mechanisms by which MSCs repair mitochondrial damage in ARDS endothelial cells are not fully understood.
Purpose of the Study:
- To investigate MSCs' ability to transfer mitochondria to pulmonary microvascular endothelial cells (MPMECs) in ARDS.
- To determine how MSC-mediated mitochondrial transfer impacts endothelial repair and vascular regeneration in ARDS.
Main Methods:
- Assessed mitochondrial transfer from MSCs to MPMECs in an ARDS model.
- Evaluated the effects of MSC-derived mitochondria on endothelial cell function, including proliferation and reactive oxygen species levels.
- Analyzed the impact on metabolic pathways like the tricarboxylic acid (TCA) cycle and fatty acid synthesis.
Main Results:
- Normal MSCs exhibited significantly higher mitochondrial transfer rates to MPMECs compared to damaged MSCs, both in vitro and in vivo.
- MSC-mediated mitochondrial transfer reduced reactive oxygen species and enhanced MPMEC proliferation.
- This transfer activated the TCA cycle and fatty acid synthesis, leading to increased vascular endothelial growth factor release and improved vascular regeneration.
Conclusions:
- MSC-mediated mitochondrial transfer is a key mechanism for repairing ARDS-affected endothelial cells.
- This transfer activates crucial metabolic pathways, promoting endothelial proliferation and vascular regeneration in ARDS.
