Neural mesenchymal-like fibroblast-derived migrasomes promote Schwann cell proliferation and migration via tenascin-C transfer during peripheral nerve regeneration

Peripheral nerve regeneration involves intricate intercellular communication between fibroblasts and Schwann cells (SCs). Migrasomes are recently identified extracellular vesicles generated in migrating cells that facilitate intercellular communication. In this study, we report that following peripheral nerve injury, neural mesenchymal-like fibroblasts (NMLFs) undergo extensive proliferation and expansion, with the concurrent production of migrasomes. These NMLF-derived migrasomes not only promote SC proliferation and migration but also act crucially as directional cues to guide SC migration. We demonstrate that mechanistically, NMLF migrasomes facilitate SC proliferation and migration through the transfer of tenascin-C (TNC). Collectively, our findings reveal a novel migrasome-mediated communication mechanism between NMLFs and Schwann cells, highlighting migrasomes as a promising therapeutic target for enhancing peripheral nerve regeneration.