中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (10): 1567-1571.doi: 10.12307/2023.363

• 干细胞基础实验 basic experiments of stem cells • 上一篇    下一篇

许旺细胞外泌体减少脊髓损伤区血管生成和瘢痕形成促进神经修复

李夏林1，胡广询1，潘大宇2   

  1. 1华中科技大学协和深圳医院脊柱外科，广东省深圳市   518052；2天津医科大学总医院骨科，天津市   300052
  • 收稿日期:2022-01-22 接受日期:2022-06-23 出版日期:2023-04-08 发布日期:2022-09-08
  • 通讯作者: 潘大宇，在读博士，天津医科大学总医院骨科，天津市 300052
  • 作者简介:李夏林，男，1978年生，湖南省醴陵市人，汉族，2014年南方医科大学毕业，博士，副主任医师，主要从事脊柱外科相关临床及基础研究。

Schwann cell-derived exosomes attenuate angiogenesis and fibrotic scar formation and promote nerve repair

Li Xialin1, Hu Guangxun1, Pan Dayu2   

  1. 1Department of Spinal Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen 518052, Guangdong Province, China; 2Department of Orthopedics, General Hospital, Tianjin Medical University, Tianjin 300052, China
  • Received:2022-01-22 Accepted:2022-06-23 Online:2023-04-08 Published:2022-09-08
  • Contact: Pan Dayu, Doctoral candidate, Department of Orthopedics, General Hospital, Tianjin Medical University, Tianjin 300052, China
  • About author:Li Xialin, MD, Associate chief physician, Department of Spinal Surgery, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen 518052, Guangdong Province, China

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摘要：

文题释义：
许旺细胞：是一种周围神经系统的神经胶质细胞，为轴突提供支持，并且形成髓鞘，其功能极其活跃，可分泌多种活性物质(如神经营养因子、细胞外基质及黏附因子等)，其分泌的物质对维持神经纤维的存活、生长及再生具有重要意义。
外泌体：其特指直径在40-100 nm的盘状囊泡。多种细胞在正常及病理状态下均可分泌外泌体。外泌体可通过其携带的蛋白质、核酸、脂类等来调节受体细胞的生物学活性，并参与到机体免疫应答、抗原提呈、细胞迁移、细胞分化、肿瘤侵袭等方面。由于外泌体能够穿透血脑屏障以及安全性的优势，已经有一些研究表明，外泌体治疗可以促进轴突再生，故而外泌体在脊髓损伤的修复领域得到了广泛关注。

背景：脊髓损伤可以导致轴突严重受损和神经元死亡，从而导致运动和/或感觉功能永久丧失。目前对于脊髓损伤的治疗手段仍然十分局限，外泌体作为一种非细胞疗法，因其强大的生物学活性而备受关注，有可能成为脊髓损伤的一种新兴治疗方案。
目的：观察许旺细胞来源外泌体对小鼠脊髓损伤后神经轴突的修复作用。
方法：将30只C57小鼠随机分成假手术组、许旺细胞来源外泌体组和PBS对照组，每组10只，对许旺细胞来源外泌体组和PBS对照组小鼠进行脊髓钳夹损伤，损伤24 h后，许旺细胞来源外泌体组小鼠尾静脉注射许旺细胞来源外泌体，PBS对照组小鼠尾静脉注射PBS，每周3次，持续4周，每次每只注射25 μL (0.1 g/L)。最后一次注射后24 h后处死小鼠，取出脊柱并分离出损伤部位上下各1 cm范围内的脊髓进行固定、脱水、包埋和切片。免疫荧光染色观察损伤区域CD31阳性血管内皮细胞和FSP1阳性成纤维细胞的募集，以及NF200阳性神经轴突存活情况。
结果与结论：与PBS对照组相比，许旺细胞来源外泌体组小鼠损伤区域中CD31阳性细胞数量减少(P < 0.01)，FSP1阳性细胞数量减少(P < 0.05)，以及NF200阳性轴突数量增加(P < 0.01)。结果表明，许旺细胞来源外泌体可以减少脊髓损伤区域内血管生成和瘢痕形成，并促进神经轴突的修复。

https://orcid.org/0000-0003-3313-9263(李夏林) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 脊髓损伤, 许旺细胞, 外泌体, 血管形成, 纤维瘢痕, 轴突

Abstract: BACKGROUND: Spinal cord injury can result in severe damage to axons and neuronal death, leading to permanent loss of motor and/or sensory function. At present, the treatment methods for spinal cord injury are still very limited. As a non-cellular therapy, exosomes have attracted much attention due to their powerful biological activities, and have the potential to become an emerging treatment option for spinal cord injury. 
OBJECTIVE: To investigate the role of Schwann cell-derived exosomes on nerve axons after spinal cord injury in mice. 
METHODS: Thirty C57 mice were randomly divided into sham group, Schwann cell-derived exosome treatment group and PBS control group (n=10 per group). The clamp injury was conducted on Schwann cell-derived exosome treatment group and PBS control group. After injury for 24 hours, the mice in the Schwann cell-derived exosome treatment group were injected with exosomes derived from Schwann cells via the caudal vein, and the mice in the PBS control group were injected with PBS via the caudal vein, three times a week for 4 weeks, 25 μL/mice (0.1 g/L) each time. Mice were sacrificed 24 hours after the last injection. After removing the spine, tissue one centimeter above and below the injury site of the spinal cord was isolated for fixation, dehydration, embedding and sectioning. The recruitment of CD31-positive vascular endothelial cells and FSP1-positive fibroblasts in the injured area, as well as the survival of NF200 positive axons was observed by immunofluorescence staining. 
RESULTS AND CONCLUSION: Compared with the PBS control group, the number of CD31-positive endothelial cells was decreased (P < 0.01) and the number of FSP1-positive fibroblasts in the injured area was decreased in the mice treated with Schwann cell-derived exosomes (P < 0.05). The number of NF200-positive axons was increased in the Schwann cell-derived exosome treatment group compared with the PBS control group (P < 0.01). These results suggest that Schwann cell-derived exosomes can reduce the recruitment of angiogenesis and scar formation cells in the area after spinal cord injury and promote the recovery of nerve axons. 

Key words: spinal cord injury, Schwann cell, exosome, angiogenesis, fibrous scar, axon

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