Mesenchymal Stem Cell-Derived Apoptotic Micro-Vesicles Repaired Sciatic Nerve Defect by Regulating Early Inflammatory...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Neuroscience

Background:

• Peripheral nerve injury (PNI) leads to an early inflammatory microenvironment (IME) that hinders nerve regeneration.
• Mesenchymal stem cells (MSCs) show therapeutic potential, but their cell-free derivatives require further investigation for PNI treatment.

Purpose of the Study:

• To elucidate the mechanism of human umbilical cord mesenchymal stem cell-derived apoptotic microvesicles (HUCMSC-Apo-mvs) in peripheral nerve repair.
• To compare the components and functions of HUCMSC-derived exosomes (Exos) and apoptotic microvesicles (Apo-mvs).
• To evaluate the therapeutic efficacy of HUCMSC-Apo-mvs in PNI models.

Main Methods:

• Comparative proteomics and miRNA sequencing of HUCMSC-Exos and HUCMSC-Apo-mvs.
• In vivo administration of HUCMSC-Apo-mvs at the PNI site.
• Assessment of macrophage polarization (M1/M2), cytokine secretion (IL-10, VEGF), angiogenesis, and neuroinflammation.
• Evaluation of Schwann cell migration and proliferation.
• Analysis of sciatic nerve regeneration and functional recovery in animal models.

Main Results:

• HUCMSC-Apo-mvs induced macrophage recruitment and shifted polarization from M1 to M2 phenotype.
• Apo-mvs promoted anti-inflammatory cytokine secretion (IL-10, VEGF), enhanced angiogenesis, and reduced neuroinflammation.
• Both Apo-mvs and Exos improved Schwann cell function, accelerating axonal regeneration and myelin remodeling.
• HUCMSC-Apo-mvs significantly improved early sciatic nerve regeneration and long-term functional recovery.

Conclusions:

• HUCMSC-Apo-mvs effectively modulate the IME for enhanced peripheral nerve repair.
• Differential components of Apo-mvs contribute to their superior efficacy over Exos in PNI.
• HUCMSC-Apo-mvs offer a promising cell-free therapeutic strategy for PNI, potentially combined with acellular grafts.