中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (4): 900-907.doi: 10.4103/1673-5374.380911

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

负载人脐带间充质干细胞外泌体的复合支架修复长距离周围神经缺损

  

  • 出版日期:2024-04-15 发布日期:2023-09-15

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Haoshuai Tang1, 2, #, Junjin Li1, 2, #, Hongda Wang1, 2, #, Jie Ren1, 2, Han Ding1, 2, Jun Shang1, 2, Min Wang3, Zhijian Wei1, 2, 4, 5, *, Shiqing Feng1, 2, 4, 5, *#br#   

  1. 1Department of Othopaedics, Tianjin Medical University General Hospital, Tianjin, China; 2International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; 3Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China; 4Department of Othopaedics, Qilu Hospital of Shandong University, Shandong University Centre for Othopedics, Advanced Medical Research Institute, Shandong University, Jinan, Shandong Province, China; 5Orthopedic Research Center of Shandong University & Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • Online:2024-04-15 Published:2023-09-15
  • Contact: Shiqing Feng, PhD, shiqingfeng@sdu.edu.cn; Zhijian Wei, PhD, weizhijian2002@126.com.
  • Supported by:
    This study was supported by the National Key Research and Development Project of Stem Cell and Transformation Research, No. 2019YFA0112100 (to SF), the National Natural Science Foundation of China No. 81930070 (to SF), Multi-fund Investment Key Projects, No. 21JCZDJC01100 (to ZW), and the Tianjin Science and Technology Planning Project, No. 22JRRCRC00010 (to SF).

摘要:

人脐带间充质干细胞通过旁分泌途径释放的外泌体被认为是其发挥神经损伤后修复作用的关键。然而在长距离周围神经缺损的修复中,局部注射或静脉注射外泌体后的疗效都不理想。实验利用一种复合神经支架负载人脐带间充质干细胞外泌体修复10mm长距离周围神经缺损。实验发现富集人脐带间充质干细胞外泌体可以促进原代培养皮质神经元轴突的生长,负载人脐带间充质干细胞外泌体的复合支架移植大鼠运动和电生理功能恢复较好,并可以有效改善肌萎缩以及肌间异常的胶原沉积。并且在移植后12周对大鼠各个器官综合安全性检测,未发现肿物或炎症的现象。说明负载人脐带间充质干细胞外泌体的复合支架在修复长距离周围神经缺损方面显示出了可继续研究转化的前景。

https://orcid.org/0000-0001-9437-7674 (Shiqing Feng); https://orcid.org/0000-0003-1094-1894 (Zhijian Wei)

关键词: 人脐带间充质干细胞, 外泌体, 神经支架, 周围神经, 周围神经损伤

Abstract: Complete transverse injury of peripheral nerves is challenging to treat. Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration. In previous studies, a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration. This three-dimensional (3D) composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly (lactic-co-glycolic acid) tube. However, whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown. In this study, we tested a comprehensive strategy for repairing long-gap (10 mm) peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes. Repair effectiveness was evaluated by sciatic functional index, sciatic nerve compound muscle action potential recording, recovery of muscle mass, measuring the cross-sectional area of the muscle fiber, Masson trichrome staining, and transmission electron microscopy of the regenerated nerve in rats. The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function, similar to autograft transplantation. More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes, which may have contributed to the observed increase in axon regeneration and distal nerve reconnection. Therefore, the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

Key words: axon growth, collagen, exosome, human umbilical cord mesenchymal stem cells, hyaluronic acid, muscular atrophy, nerve guidance conduits, peripheral nerve regeneration