Schwann cell‐derived exosomes enhance axonal regeneration in the peripheral nervous system

TLDR

Schwann cells support peripheral axonal regeneration by dedifferentiating after injury, guiding axons, and engaging in contact and soluble factor crosstalk. The study proposes that Schwann cell exosomes locally support axonal maintenance and regeneration after nerve damage. SC-derived exosomes promote a pro‑regenerating growth‑cone phenotype by reducing RhoA activity, thereby preventing growth‑cone collapse. The authors demonstrate that Schwann cell exosomes are internalized by axons, enhance axonal regeneration in vitro and in vivo, and reveal a novel communication mechanism during regeneration. GLIA 2013;61:1795–1806.

Abstract

Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor‐like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano‐vesicles known as exosomes which are specifically internalized by axons. Surprisingly, SC‐derived exosomes markedly increase axonal regeneration in vitro and enhance regeneration after sciatic nerve injury in vivo . Exosomes shift the growth cone morphology to a pro‐regenerating phenotype and decrease the activity of the GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether, our work identifies a novel mechanism by which SCs communicate with neighboring axons during regenerative processes. We propose that SC exosomes represent an important mechanism by which these cells locally support axonal maintenance and regeneration after nerve damage. GLIA 2013;61:1795–1806