Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair.
BACKGROUND
Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo.


METHODS
Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated.


RESULTS
M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs.


CONCLUSIONS
M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration.
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. Electronic address: zhchuansy@163.com.
Chuan
C
Zhan
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Cheng-bin
CB
Ma
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Hong-mou
HM
Yuan
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Bao-yuan
BY
Cao
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Jia-jun
JJ
Zhu
D000818:Animals; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009416:Nerve Regeneration; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology*
D035683:MicroRNAs; C525067:MIR223, human
Macrophage phenotype; Microvesicles; Nerve regeneration; Schwann cell