Schwann Cell-Derived Exosomes Enhance Axonal Regeneration in the Peripheral Nervous System

被引:328
作者
Alejandra Lopez-Verrilli, Maria [1 ]
Picou, Frederic [1 ]
Court, Felipe A. [1 ,2 ]
机构
[1] Pontificia Univ Catolica Chile, Fac Biol Sci, Millennium Nucleus Regenerat Biol, Santiago, Chile
[2] Neuroun Biomed Fdn, Santiago, Chile
关键词
Schwann cell; exosomes; axonal regeneration; nerve injury; PROTEIN-SYNTHESIS; DEGENERATION; GLIA; RHOA; OLIGODENDROCYTES; CYTOSKELETON; PARTNERSHIP; INHIBITION; MORPHOLOGY; RIBOSOMES;
D O I
10.1002/glia.22558
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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
引用
收藏
页码:1795 / 1806
页数:12
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