Combination of G-CSF Administration and Human Amniotic Fluid Mesenchymal Stem Cell Transplantation Promotes Peripheral Nerve Regeneration
Combination of G-CSF Administration and Human Amniotic Fluid Mesenchymal Stem Cell Transplantation Promotes Peripheral Nerve Regeneration
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DOI：
10.1007/s11064-008-9815-5
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Wang, Yeou-Chih
中科院分区：
文献类型：
--
作者：
Pan, Hung-Chuan;Chen, Chung-Jung;Wang, Yeou-Chih
羊水间充质干细胞（Amniotic fluid mesenchymal stem cells，AFS）具有通过分泌遗传性神经营养因子（neurotrophic factor，NGF）改善周围神经损伤的潜能，但存在移植后存活时间短的缺点。粒细胞集落刺激因子（G-CSF）具有多种功能，包括抗炎和抗凋亡作用。本研究旨在探讨G-CSF是否能增强AFS对周围神经损伤的保护作用。还研究了抗炎/抗凋亡作用的潜在参与。用血管夹夹伤大鼠左侧坐骨神经，造成周围神经损伤。将AFS包埋在纤维蛋白胶中并递送到损伤部位。G-CSF（50 μ g/kg）通过腹膜内注射连续给药7天。损伤后7天或28天评价细胞凋亡、炎性细胞因子、运动功能和神经再生。挤压伤引起坐骨神经炎症反应，破坏神经完整性，损害神经功能。挤压伤引起的炎症在接受G-CSF的组中减弱，但在仅AFS的组中没有减弱。在移植的AFS中，检测到明显的细胞凋亡，并且G-CSF治疗可以减少这种情况。在AFS移植组、G-CSF组和AFS/G-CSF联合治疗组中观察到神经髓鞘形成增加和运动功能改善。值得注意的是，联合治疗显示出最有益的效果。总之，与G-CSF的AFS的伴随治疗增强周围神经再生，这可能涉及抑制植入的AFS中的凋亡性死亡和炎症反应的衰减。
Amniotic fluid mesenchymal stem cells (AFS) harbor the potential to improve peripheral nerve injury by inherited neurotrophic factor secretion, but present the drawback of the short-term survival after transplantation. Granulocyte-colony stimulating factor (G-CSF) has a diversity of functions, including anti-inflammatory and anti-apoptotic effects. This study was conducted to evaluate whether G-CSF could augment the neuroprotective effect of transplanted AFS against peripheral nerve injury. The potential involvement of anti-inflammation/anti-apoptosis effect was also investigated. Peripheral nerve injury was produced in Sprauge-Dawley rats by crushing left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. G-CSF (50 mu g/kg) was administrated by intra-peritoneal injection for 7 consecutive days. Cell apoptosis, inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. Crush injury induced inflammatory response, disrupted nerve integrity, and impaired nerve function in sciatic nerve. Crush injury-provoked inflammation was attenuated in groups receiving G-CSF but not in AFS only group. In transplanted AFS, marked apoptosis was detected and this event was reduced by G-CSF treatment. Increased nerve myelination and improved motor function were observed in AFS transplanted, G-CSF administrated, and AFS/G-CSF combined treatment groups. Significantly, the combined treatment showed the most beneficial effect. In conclusion, the concomitant treatment of AFS with G-CSF augments peripheral nerve regeneration which may involve the suppression of apoptotic death in implanted AFS and the attenuation of inflammatory response.