中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (9): 1990-1998.doi: 10.4103/1673-5374.366497

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

负载胰岛素生长因子1预处理神经干细胞来源的外泌体的低温3D打印胶原/壳聚糖支架促进创伤性脑损伤后的神经再生

  

  • 出版日期:2023-09-15 发布日期:2023-03-06
  • 基金资助:
    国家科技重大专项课题

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury

Xiao-Yin Liu1, 2, #, Yin-He Feng3, #, Qing-Bo Feng4, #, Jian-Yong Zhang5, Lin Zhong6, Peng Liu1, Shan Wang1, Yan-Ruo Huang7, *, Xu-Yi Chen2, 8, *, Liang-Xue Zhou1, *#br#   

  1. 1Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China; 2Tianjin Key Laboratory of Neurotrauma Repair, Pingjin Hospital Brain Center, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, China; 3Department of Respiratory and Critical Care Medicine, People’s Hospital of Deyang City, Affiliated Hospital of Chengdu College of Medicine, Deyang, Sichuan Province, China; 4Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Province, China; 5Department of General Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China; 6The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China; 7Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China; 8Institute of Medical Security for Maritime Rights Protection of Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, China
  • Online:2023-09-15 Published:2023-03-06
  • Contact: Liang-Xue Zhou, MD, zhlxlll@163.com; Xu-Yi Chen, MD, chenxuyi1979@126.com; Yan-Ruo Huang, MD, huangyanruo@126.com.
  • Supported by:
    This work was supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development, No. 2019ZX09301-147 (to LXZ).

摘要:

虽然临床已有包括手术、药物治疗和康复治疗在内的多种方法治疗创伤性脑损伤,但治疗效果仍不十分令人满意。 已有研究提出应用组织工程的手段可改善创伤性脑损伤的治疗效果。 实验应用一种新型的组织工程支架--负载胰岛素生长因子1预处理神经干细胞来源的外泌体的低温3D打印胶原/壳聚糖支架修复创伤性脑损伤大鼠脑组织空洞。该复合支架可以持续释放外泌体2周。免疫荧光染色和透射电镜显示,该复合支架植入可促进内源性神经干细胞的募集和神经再生,改善血管生成,抑制炎症和细胞凋亡,改善损伤区域受损神经组织的恢复。Morris水迷宫测试和改良神经功能评分显示该复合支架植入可改善创伤性脑损伤大鼠的运动和认知功能。这些数据表明负载胰岛素生长因子1预处理神经干细胞来源的外泌体的低温3D打印胶原/壳聚糖支架为创伤性脑损伤的治疗提供了潜在的策略。

https://orcid.org/0000-0001-9991-6358 (Liang-Xue Zhou); https://orcid.org/0000-0002-0420-8349 (Xu-Yi Chen); https://orcid.org/0000-0001-7106-590X (Yan-Ruo Huang)

Abstract: There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Key words: 3D printing, angiogenesis, chitosan, collagen, exosomes, functional recovery, insulin-like growth factor-1, neural regeneration, neural stem cells, traumatic brain injury