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GliaVolume 61, Issue 11 Original Article Schwann cell‐derived exosomes enhance axonal regeneration in the peripheral nervous system María Alejandra Lopez‐Verrilli

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Search for more papers by this author Frederic Picou

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Search for more papers by this author Felipe A. Court

Corresponding Author

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Neurounion Biomedical Foundation, Santiago, Chile

Address correspondence to Felipe A. Court, Av. B. O\'Higgins 340/Casilla 114‐D, Santiago 8331150, Chile. E‐mail:

fcourt@bio.puc.cl

Search for more papers by this author María Alejandra Lopez‐Verrilli

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Search for more papers by this author Frederic Picou

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Search for more papers by this author Felipe A. Court

Corresponding Author

Millennium Nucleus for Regenerative Biology, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

Neurounion Biomedical Foundation, Santiago, Chile

Address correspondence to Felipe A. Court, Av. B. O\'Higgins 340/Casilla 114‐D, Santiago 8331150, Chile. E‐mail:

fcourt@bio.puc.cl

Search for more papers by this author

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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

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