Source-Dependent Mitochondrial Transplantation Drives Schwann Cell Bioenergetic Reprogramming and Peripheral Nerve
Xiangling Li1, Yunjie Huang1, Xiaojian Cao1
1Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Advanced Healthcare Materials
|July 29, 2026
Summary
Mitochondrial transplantation (MT) enhances peripheral nerve repair by reprogramming Schwann cell metabolism, not just energy supply. This improves axonal regeneration and functional recovery, with mesenchymal stem cell-derived mitochondria showing greater efficacy.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Peripheral nerve injury (PNI) triggers Schwann cell (SC) metabolic changes crucial for nerve repair.
- Mitochondrial transplantation (MT) is a potential therapy, but its mechanism beyond energy supply is unclear.
Purpose of the Study:
- Compare effects of mitochondria from induced pluripotent stem cells (iPSCs) versus induced mesenchymal stem cells (iMSCs) on SC metabolism and nerve regeneration.
- Investigate if MT's benefits stem from metabolic reprogramming or transient energy provision.
Main Methods:
- Systematic comparison of iPSC-derived MT (iP-MT) and iMSC-derived MT (iM-MT) in SCs.
- Assessment of SC metabolism, proliferation, migration, and neurotrophic/antioxidant functions.
- Evaluation of MT efficacy in a rat sciatic nerve injury model, measuring regeneration and functional recovery.
Main Results:
- Exogenous mitochondria were uptaken by SCs, boosting ATP production and membrane potential.
- MT reshaped SC metabolism, favoring glycolysis and oxidative phosphorylation, enhancing cell functions and antioxidant capacity.
- MT significantly improved axonal regeneration, remyelination, and functional recovery in vivo.
- iM-MT exhibited superior metabolic adaptability and therapeutic outcomes, reducing oxidative stress and apoptosis.
Conclusions:
- Mitochondrial transplantation promotes peripheral nerve repair through metabolic reprogramming of Schwann cells.
- MT's therapeutic effects extend beyond energy supplementation, involving enhanced cellular functions and stress resistance.
- Mesenchymal stem cell-derived mitochondria offer a promising therapeutic strategy for peripheral nerve regeneration due to their metabolic adaptability.
