中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (10): 1903-1911.doi: 10.4103/1673-5374.280330

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

嗅鞘细胞与人脐带间充质干细胞来源外泌体协同促进坐骨神经的再生

  

  • 出版日期:2020-10-15 发布日期:2020-08-19
  • 基金资助:

    国家自然科学基金面上项目（81872699），陕西省重点项目（2017ZDXM-SF-043），军事医学科技青年发展计划项目（19QNP061）

Combination of olfactory ensheathing cells and human umbilical cord mesenchymal stem cell-derived exosomes promotes sciatic nerve regeneration

Yang Zhang1, Wen-Tao Wang2, Chun-Rong Gong3, Chao Li4, Mei Shi1   

  1. 1 Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi Province, China
    2 Department of Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, China
    3 Rehabilitation Center, North District Hospital of the People’s Hospital of Lin Yi City, Linyi, Shandong Province, China
    4 Department of Orthopedics, The Eighth Medical Center of Chinese PLA general Hospital, Beijing, China
  • Online:2020-10-15 Published:2020-08-19
  • Contact: Mei Shi, PhD, mshi82@hotmail.com; Chao Li, PhD, Chnmedli@126.com.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, No. 81872699 (to MS), Key project of Shaanxi Province, China, No. 2017ZDXM-SF-043 (to MS), and the Military Medical Science and Technology Youth Development Program, China, No. 19QNP061 (to CL).

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摘要：

嗅鞘细胞是一种可用于神经再生的种子细胞，其应用受到局部缺氧环境的限制。提取自人脐带间充质干细胞的外泌体已成为调节缺氧病理过程的潜在策略之一，然而其对嗅鞘细胞迁移能力等生物学功能的影响尚不清楚，尤其是在低氧环境中，且嗅鞘细胞和外泌体对周围神经损伤修复的协同作用也不清楚。因此，解决上述问题能够增强嗅鞘细胞在神经损伤治疗中的生物学作用。实验从大鼠嗅球中提取嗅鞘细胞，以0-400 μg/mL人脐带间充质干细胞来源的外泌体干预嗅鞘细胞12-48h，发现以400 μg/mL外泌体干预24h，可明显促进嗅鞘细胞活性和增值能力。然后观察外泌体干预的嗅鞘细胞在缺氧24h后性能的变化，发现外泌体可明显促进缺氧嗅鞘细胞的存活和迁移，且有效增加细胞中脑源性神经营养因子基因及蛋白的表达与分泌。最后通过左侧坐骨神经12mm缺损大鼠模型，证实嗅鞘细胞与外泌体可协同促进损伤坐骨神经的运动与感觉功能。表明嗅鞘细胞联合人脐带间充质干细胞源性外泌体具有促进神经再生和功能恢复的能力。动物手术已于2018年10月7日获得空军医科大学伦理委员会的批准（批准号IACUC-20181004）；人体组织使用于2019年5月20日经临沂市人民医院伦理委员会批准（批准号30054）。

orcid: 0000-0002-4937-405X (Mei Shi) 

         0000-0001-7135-2503 (Chao Li)

关键词: 坐骨神经损伤, 嗅鞘细胞, 人脐带间充质干细胞, 外泌体, 细胞迁移, 缺氧, 神经再生, 神经功能, 脑源性神经营养因子

Abstract: Olfactory ensheathing cells (OECs) are promising seed cells for nerve regeneration. However, their application is limited by the hypoxic environment usually present at the site of injury. Exosomes derived from human umbilical cord mesenchymal stem cells have the potential to regulate the pathological processes that occur in response to hypoxia. The ability of OECs to migrate is unknown, especially in hypoxic conditions, and the effect of OECs combined with exosomes on peripheral nerve repair is not clear. Better understanding of these issues will enable the potential of OECs for the treatment of nerve injury to be addressed. In this study, OECs were acquired from the olfactory bulb of Sprague Dawley rats. Human umbilical cord mesenchymal stem cell-derived exosomes (0–400 μg/mL) were cultured with OECs for 12–48 hours. After culture with 400 μg/mL exosomes for 24 hours, the viability and proliferation of OECs were significantly increased. We observed changes to OECs subjected to hypoxia for 24 hours and treatment with exosomes. Exosomes significantly promoted the survival and migration of OECs in hypoxic conditions, and effectively increased brain-derived neurotrophic factor gene expression, protein levels and secretion. Finally, using a 12 mm left sciatic nerve defect rat model, we confirmed that OECs and exosomes can synergistically promote motor and sensory function of the injured sciatic nerve. These findings show that application of OECs and exosomes can promote nerve regeneration and functional recovery. This study was approved by the Institutional Ethical Committee of the Air Force Medical University, China (approval No. IACUC-20181004) on October 7, 2018; and collection and use of human umbilical cord specimens was approved by the Ethics Committee of the Linyi People’s Hospital, China (approval No. 30054) on May 20, 2019.

Key words: brain-derived neurotrophic factor, cell migration, cell viability, functional recovery, hypoxia, nerve regeneration, sciatic functional index, sciatic nerve injury