Extracellular Vesicles From Mesenchymal Stromal Cells Drive Muscle and Neuronal Regeneration Through TNFα Modulation.

Area of Science:

• Regenerative Medicine
• Cell Biology
• Neuroscience

Background:

• Muscle defects impact patients of all ages, necessitating effective regeneration strategies.
• Mesenchymal stromal/stem cell-derived extracellular vesicles (EVs) show promise for neural-muscle regeneration, but their mechanism is unclear.

Purpose of the Study:

• To elucidate the in vivo mechanism of EV-mediated neural-muscle regeneration using advanced 3D models.
• To investigate EV effects on neuroinflammation and neural repair.

Main Methods:

• Utilized 3D engineered human muscle tissue (decellularized ECM with hMPC and macrophages) and organotypic rat spinal cord models.
• Assessed neuroinflammation in 2D primary microglia models stimulated with LPS.
• Analyzed functional outcomes, protein, and gene expression of GMP-grade EV-treated samples.

Main Results:

• EVs protected muscle precursor cells from damage-induced death and promoted proliferation.
• EV treatment downregulated TNFα, a key factor in inflammation and cell death.
• EVs inhibited neuroinflammation and promoted neural axon sprouting in both microglia and spinal cord models.

Conclusions:

• Extracellular vesicles (EVs) hold significant potential for tissue regeneration.
• EVs exert therapeutic effects by modulating TNFα, thereby promoting both muscle and neural regeneration.