Cdc42-Modified BMSC-Derived exosomes promote acellular nerve allografts to bridge sciatic nerve defects

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Neuroscience

Background:

• Peripheral nerve injury (PNI) leads to lasting functional impairments, with current treatments being insufficient.
• Tissue engineering offers a promising avenue for nerve repair and functional recovery.

Purpose of the Study:

• To develop and evaluate a novel tissue-engineered graft combining Cdc42-modified bone marrow-derived mesenchymal stem cell (BMSC)-derived exosomes (Exos-Cdc42) with an acellular nerve allograft (ANA) for enhanced nerve regeneration.
• To assess the in vitro and in vivo therapeutic potential of Exos-Cdc42 loaded ANA for peripheral nerve repair.

Main Methods:

• Exosomes were isolated from BMSCs and modified for Cdc42 overexpression (Exos-Cdc42).
• In vitro studies assessed Exos-Cdc42 effects on Schwann cell behavior and gene expression.
• In vivo studies evaluated the therapeutic efficacy of Exos-Cdc42 loaded ANA in a rat sciatic nerve injury model, analyzing functional recovery and nerve histology.

Main Results:

• Exos-Cdc42 significantly promoted Schwann cell proliferation, migration, and secretion of neurotrophic factors (BDNF, NGF, CNTF) in vitro.
• In vivo, the Exos-Cdc42 + ANA treatment group showed improved sciatic nerve functional recovery, evidenced by higher functional index scores and increased muscle weight.
• Histological analysis revealed enhanced axonal regeneration and myelination, with thicker myelin sheaths and larger axon diameters in the treatment group.

Conclusions:

• The combination of Exos-Cdc42 with ANA significantly enhances peripheral nerve regeneration and functional recovery.
• Exos-Cdc42 promotes Schwann cell-mediated repair responses, improving the therapeutic efficacy of acellular nerve allografts.
• This strategy represents a promising approach for treating peripheral nerve injuries.