中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (4): 651-658.doi: 10.4103/1673-5374.155442

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

人脐带间充质干细胞的旁分泌可促进损伤周围神经修复

  

  • 收稿日期:2015-02-10 出版日期:2015-04-22 发布日期:2015-04-22
  • 基金资助:

    国家自然科学基金项目（31100696，31170946），863项目（2012AA020502），973项目(2014CB542201)，北京市科技新星（2011115）

     

Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

Zhi-yuan Guo 1, Xun Sun 1, Xiao-long Xu 1, Qing Zhao 1, Jiang Peng 1, 2, Yu Wang 1, 2,   

  1. 1 Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China
    2 The Neural Regeneration Co-innovation Center of Jiangsu Province, Nantong, Jiangsu Province, China
  • Received:2015-02-10 Online:2015-04-22 Published:2015-04-22
  • Contact: Yu Wang, M.D., wangwangdian628@126.com
  • Supported by:

    This research was supported by the National Natural Science Foundation of China, No. 31100696, 31170946; a grant from the National High Technology Research and Development Program of China (863 Program), No. 2012AA020502; a grant from the National Program on Key Basic Research Project of China (973 Program), No. 2014CB542201; and a grant from Beijing Metropolis Beijing Nova Program, No. 2011115.

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摘要：

既往有研究认为干细胞修复周围神经损伤的主要机制是分泌一些神经生长因子和细胞外基质，构建适宜轴突再生的微环境，从而促进损伤神经的再生。我们为进一步揭示人脐带间充质干细胞旁分泌机制对神经再生的潜在影响，实验首先以人细胞因子抗体芯片分析发现人脐带间充质干细胞表达14种重要的神经营养因子，继而以ELISA检测和免疫组化证实脑源性神经营养因子、胶质细胞源性神经营养因子、肝细胞生长因子、神经营养因子3、碱性成纤维细胞生长因子Ⅰ型胶原、纤维连接蛋白和层粘连蛋白水平较高。然后以人脐带间充质干细胞条件培养基培养许旺细胞，发现其可促进许旺细胞存活和增殖，并促进许旺细胞中神经营养因子和脑源性神经营养因子的表达以及背根神经节外植体轴突的生长。提示人脐带间充质干细胞旁分泌作用可促进损伤周围神经的修复。

关键词: 神经再生, 人脐带间充质干细胞, 条件培养基, 许旺细胞, 背根神经节, 轴突, 神经营养因子, 周围神经再生

Abstract:

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

Key words: nerve regeneration, human umbilical cord-derived mesenchymal stem cells, conditioned medium, Schwann cells, dorsal root ganglion, axons, peripheral nerve regeneration, neurotrophic factors, neural regeneration