中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1118-1123.doi: 10.4103/1673-5374.355817

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

加载活化许旺细胞的人发角蛋白骨架构建新型人工神经移植物可桥接修复周围神经缺损

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    军事医学科技青年培训计划项目(19QNP005);南方医科大学南方医院院长基金项目(2020B028)

Artificial nerve graft constructed by coculture of activated Schwann cells and human hair keratin for repair of peripheral nerve defects

Han-Jun Qin1, #, Hang Li2, #, Jun-Ze Chen3, Kai-Rui Zhang1, Xing-Qi Zhao1, Jian-Qiang Qin4, Bin Yu1, *, Jun Yang1, 5, *   

  1. 1Department of Orthopedics, Nanfang Hospital, Southern Medical University; Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;  2Hebei Medical University, Shijiazhuang, Hebei Province, China;  3Department of Orthopedics, Baiyun Branch of Southern Hospital, Guangzhou, Guangdong Province, China;  4Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China;  5Department of Orthopedics, The 74th Group Military Hospital of PLA, Guangzhou, Guangdong Province, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Jun Yang, PhD, yangjun201911@sina.com; Bin Yu, PhD, yubin@smu.edu.cn.
  • Supported by:
    The study was supported by Military Medical Science & Technology Youth Training Program, No. 19QNP005; and President Foundation of Nanfang Hospital, Southern Medical University, No. 2020B028 (both to JY).

摘要:

既往研究发现,人发角蛋白具有无抗原性的特点,且机械性能优良。许旺细胞作为周围神经系统独特的神经胶质细胞,经白细胞介素1β诱导可分泌神经生长因子,促进神经再生。因此若能在人发角蛋白骨架中加载许旺细胞,可能会更有效地修复神经缺损。因此实验构建了一种人发角蛋白骨架上加载活化的许旺细胞的人工神经移植物,发现纵向人发角蛋白微丝结构为许旺细胞提供粘附介质、空间和方向,并促进许旺细胞的生长和神经纤维的再生。此外白细胞介素1β不仅能激活许旺细胞,还能增强其活性,促进神经生长因子的表达。被激活的许旺细胞能进一步活化巨噬细胞,而后者可产生白细胞介素1β,能维持许旺细胞的活性,形成了一种良性循环,并促进了神经修复。进一步体内研究发现,这种人工神经移植物可有效促进坐骨神经损伤大鼠神经传导功能和运动功能明显改善,且促进神经修复因子成纤维细胞生长因子2和人转化生长因子B受体2的表达。提示这种人工神经移植物可有效修复周围神经损伤。

https://orcid.org/0000-0002-9982-6157 (Han-Jun Qin)

关键词: 人发角蛋白, 生物活性, 人工神经移植物, 许旺细胞, 巨噬细胞, 白细胞介素1β, 周围神经损伤, 神经生长因子, 神经修复, 神经移植

Abstract: Studies have shown that human hair keratin (HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.

Key words: artificial nerve graft, bioactive, human hair keratin, interleukin-1β, macrophages, nerve graft, nerve growth factor, nerve repair, peripheral nervous injury, Schwann cells