Effects of the in vivo predegenerated nerve graft on early Schwann cell migration: quantitative analysis using S100-GFP mice.
In peripheral nerve transection injury, continuity of axons as well as that of the basal lamina is disconnected. In such case, migrating Schwann cells (SCs) would be the only axonal guidance at an early stage of regeneration. However, it takes a few days for the dedifferentiated SCs to start migration, while axonal growth begins a few hours after injury. Consequently, the axons without guidance extensively branch out and wander off at the lesion, resulting in aberrant reinnervation. Therefore, enhancing SCs migration could be an attractive therapeutic strategy. In this study, we investigated the effects of the in vivo nerve predegeneration on SC migration and the time course of these changes. In our analysis, we established a novel animal model by nerve transplantation from S100-GFP mice (in which SCs constitutively express green fluorescent protein driven by the S100B promoter), by which SC migration could be exclusively visualized. Our results showed that SCs acquire the maximal migration ability with 14-day predegeneration, but subsequently it gradually decreased. There was a correlation between the time course of the changes in SC migration and the number of activated macrophages. These findings suggest that using predegenerated nerve grafts in repairing the transected nerves could facilitate SC migration into the recipient nerve stump. This technique could be beneficial for early establishment of axonal guidance and possible functional improvement after transection injury.
Tomita
Koichi
K
Department of Plastic Surgery, Osaka University, Graduate School of Medicine, 2-2 C11 Yamadaoka, Suita-shi, Osaka 565-0871, Japan. tomita@psurg.med.osaka-u.ac.jp
Hata
Yuki
Y
Kubo
Tateki
T
Fujiwara
Toshihiro
T
Yano
Kenji
K
Hosokawa
Ko
K
D000818:Animals; D001369:Axons / Q000502:physiology; D002465:Cell Movement; D049452:Green Fluorescent Proteins / Q000235:genetics*; D066298:In Vitro Techniques; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009410:Nerve Degeneration / Q000473:pathology*; D009414:Nerve Growth Factors / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics*; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology / Q000637:transplantation*; D013997:Time Factors
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; C579158:S100b protein, rat; D049452:Green Fluorescent Proteins