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
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Barrientos, Sebastian A.
Martinez, Nicolas W.
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Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Martinez, Nicolas W.
Yoo, Soonmoon
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机构:
Alfred I duPont Hosp Children, Nemours Biomed Res Inst, Wilmington, DE 19716 USACatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Yoo, Soonmoon
Jara, Juan S.
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Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Jara, Juan S.
Zamorano, Sebastian
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Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell, Santiago 8380453, Chile
Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 8380453, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Zamorano, Sebastian
Hetz, Claudio
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机构:
Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell, Santiago 8380453, Chile
Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 8380453, Chile
Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
NeuroUnion Biomed Fdn, Santiago 7630614, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Hetz, Claudio
Twiss, Jeffery L.
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h-index: 0
机构:
Drexel Univ, Dept Biol, Philadelphia, PA 19104 USACatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Twiss, Jeffery L.
Alvarez, Jaime
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Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Alvarez, Jaime
Court, Felipe A.
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h-index: 0
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Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
NeuroUnion Biomed Fdn, Santiago 7630614, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Barrientos, Sebastian A.
Martinez, Nicolas W.
论文数: 0引用数: 0
h-index: 0
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Martinez, Nicolas W.
Yoo, Soonmoon
论文数: 0引用数: 0
h-index: 0
机构:
Alfred I duPont Hosp Children, Nemours Biomed Res Inst, Wilmington, DE 19716 USACatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Yoo, Soonmoon
Jara, Juan S.
论文数: 0引用数: 0
h-index: 0
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Jara, Juan S.
Zamorano, Sebastian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell, Santiago 8380453, Chile
Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 8380453, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Zamorano, Sebastian
Hetz, Claudio
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chile, Fac Med, Inst Biomed Sci, Ctr Mol Studies Cell, Santiago 8380453, Chile
Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 8380453, Chile
Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
NeuroUnion Biomed Fdn, Santiago 7630614, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Hetz, Claudio
Twiss, Jeffery L.
论文数: 0引用数: 0
h-index: 0
机构:
Drexel Univ, Dept Biol, Philadelphia, PA 19104 USACatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Twiss, Jeffery L.
Alvarez, Jaime
论文数: 0引用数: 0
h-index: 0
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
Alvarez, Jaime
Court, Felipe A.
论文数: 0引用数: 0
h-index: 0
机构:
Catholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile
NeuroUnion Biomed Fdn, Santiago 7630614, ChileCatholic Univ Chile, Dept Physiol, Fac Biol, Santiago 8331150, Chile