中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1068-1077.doi: 10.4103/1673-5374.300458

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

复合神经干细胞的胶原/硫酸肝素多孔支架可改善创伤性脑损伤大鼠的神经功能

  

  • 出版日期:2021-06-15 发布日期:2020-12-31
  • 基金资助:

    这项工作得到了国家自然科学基金项目（11672332, 11932013）；国家重点研发计划（2016YFC101500）；天津市重点科技支撑基金（17YFZCSY00620）

Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury

Jian Zhang1, 2, #, Ren-Jie Wang1, #, Miao Chen3, Xiao-Yin Liu4, Ke Ma1, 2, Hui-You Xu1, 2, Wu-Sheng Deng1, Yi-Chao Ye1, 2, Wei-Xin Li2, Xu-Yi Chen1, *, Hong-Tao Sun1, *   

  1. 1 Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, China;  2 Graduate School, Logistics University of People’s Armed Police Force, Tianjin, China;  3 Graduate School, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China;  4 Graduate School, Tianjin Medical University, Tianjin, China
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Hong-Tao Sun, PhD, zhangjian19237@126.com; Xu-Yi Chen, PhD, chenxuyi1979@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 11672332, 11932013 (both to XYC); the National Key Research and Development Plan of China, No. 2016YFC1101500 (to HTS); the Key Science and Technology Support Foundation of Tianjin of China, No. 17YFZCSY00620 (to HTS).

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摘要：

单纯干细胞移植治疗创伤性脑损伤的效果欠佳的原因是外源性神经干细胞无法有效迁移到局部损伤部位，使得神经干细胞在损伤部位的粘附和增殖效果极差。为增强外源性干细胞向损伤区的靶向传递，细胞治疗与神经组织工程技术相结合有望成为创伤性脑损伤治疗的新策略。实验采用冻干法制备胶原/硫酸肝素多孔支架具有稳定的理化性能，其高孔隙率适宜于神经干细胞的增殖和迁移，具备良好的细胞生物相容性。以这种复合神经干细胞的胶原/硫酸肝素多孔支架移植治疗打击法构建的创伤性脑损伤模型大鼠，结果显示，经这种支架移植治疗2个月后，损伤脑组织中神经元、神经纤维、突触和髓鞘的再生得到显著改善，脑水肿和细胞凋亡明显减轻，大鼠的运动及认知功能出现明显的恢复。提示这种新型的复合神经干细胞的胶原/硫酸肝素多孔支架可促进创伤性脑损伤大鼠神经功能的恢复。实验于2019年2月10日经武警医疗中心伦理委员会批准，批准号2017-0007.2。

https://orcid.org/0000-0003-2076-3606 (Jian Zhang)

关键词:

创伤性脑损伤, 支架, 胶原, 硫酸肝素, 神经干细胞, 损伤, 修复, 再生

Abstract: One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site, resulting in poor adhesion and proliferation of neural stem cells at the injured area. To enhance the targeted delivery of exogenous stem cells to the injury site, cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury. Collagen/heparan sulfate porous scaffolds, prepared using a freeze-drying method, have stable physical and chemical properties. These scaffolds also have good cell biocompatibility because of their high porosity, which is suitable for the proliferation and migration of neural stem cells. In the present study, collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury, which was established using the controlled cortical impact method. At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells, there was significantly improved regeneration of neurons, nerve fibers, synapses, and myelin sheaths in the injured brain tissue. Furthermore, brain edema and cell apoptosis were significantly reduced, and rat motor and cognitive functions were markedly recovered. These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury. This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force, China (approval No. 2017-0007.2) on February 10, 2019.

Key words: collagen, heparan sulfate, injury, neural stem cells, regeneration, repair, scaffold, traumatic brain injury, morris water maze, motor evoked potential, synapses, myelin sheaths