Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis

Redox Biology, 2023 · DOI: https://doi.org/10.1016/j.redox.2023.102871 · Published: September 7, 2023

Simple Explanation

Spinal cord injury (SCI) leads to nerve cell death, and one type of cell death called ferroptosis plays a role. This study found that in SCI, nerve cells undergo ferroptosis, and this is linked to problems in how mitochondria (the cell's energy producers) are managed. Mesenchymal stem cells (MSCs) can transfer healthy mitochondria to damaged nerve cells. This transfer helps restore the nerve cells' mitochondrial function, reducing ferroptosis and aiding recovery from SCI. The research suggests a new approach to treating SCI, using stem cells to deliver healthy mitochondria to injured nerve cells, which could help improve recovery.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Neurons primarily suffer from ferroptosis in SCI, as shown by single-cell RNA sequencing.
2
MSCs transfer mitochondria to neurons via tunneling nanotubes, restoring mitochondrial homeostasis by fusing with neuronal mitochondria.
3
MSCs effectively inhibit ferroptosis and improve functional recovery after SCI through mitochondrial transfer, as demonstrated in vivo.

Research Summary

This study investigates the role of mitochondrial quality control (MQC) in neuronal ferroptosis after spinal cord injury (SCI) and the therapeutic potential of mesenchymal stem cells (MSCs). The research demonstrates that neurons primarily undergo ferroptosis in SCI and that disordered MQC aggravates this process through excessive mitochondrial fission and mitophagy. MSCs-mediated mitochondrial transfer restores neuronal mitochondrial pool and inhibits ferroptosis through mitochondrial fusion, offering a promising clinical translation strategy for mitochondria-related CNS disorders.

Practical Implications

Clinical Translation Strategy

Stem cell-mediated mitochondrial therapy shows promise for treating mitochondria-related central nervous system disorders.

Therapeutic Target Identification

Targeting mitochondrial quality control mechanisms could restore mitochondrial homeostasis and alleviate neuronal ferroptosis after SCI.

Delivery Vector Potential

MSCs can serve as effective delivery vectors for mitochondrial transplantation-based therapy of SCI.

Study Limitations

1
The possibility of reverse direction of mitochondrial transfer from neurons to MSCs is required investigation in detail.
2
Whether the neuron-to-neuron mitochondrial exchange can synergize the beneficial effect of MSC-to-neuron mitochondrial transfer is worth further exploring.
3
Prolonged therapeutic effects on neuronal regeneration of MSCs in the chronic phase deserves consideration.

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