中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (7): 1172-1179.doi: 10.4103/1673-5374.187061

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

人脐带干细胞来源的细胞外基质能更好的促进周围神经再生?

  

  • 出版日期:2016-07-30 发布日期:2016-07-30
  • 基金资助:
    国家自然科学基金(批准no.31170946);973计划项目(2012cb518106号2014cb542201); “第十二个五年计划”,中国人民解放军医学科学发展项目(bws13c029)

Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration

Bo Xiao1, 2, 3, #, Feng Rao4, #, Zhi-yuan Guo5, Xun Sun1, 2, Yi-guo Wang1, 2, Shu-yun Liu1, 2, Ai-yuan Wang1, 2, Quan-yi Guo1, 2, Hao-ye Meng1, 2, Qing Zhao1, 3, Jiang Peng1, 3, Yu Wang1, 3, *, Shi-bi Lu1, 2, *   

  1. 1 Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China 2 Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Beijing, China 3 The Neural Regeneration Co-innovation Center of Jiangsu Province, Nantong, Jiangsu Province, China 4 Department of Orthopedics, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, China 5 Department of Orthopedics, Cangzhou Central Hospital, Cangzhou, Hebei Province, China
  • Online:2016-07-30 Published:2016-07-30
  • Contact: Yu Wang, Ph.D. or Shi-bi Lu, M.D., wangwangdian628@126.com or shibilu94@163.com
  • Supported by:
    This research was supported by the National Natural Science Foundation of China, Grant No. 31170946; the National Program on Key Basic Research Project of China (973 Program), Grant No. 2012CB518106 and No. 2014CB542201; and the Special Project of the “Twelfth Five-year Plan” for Medical Science Development of PLA, No. BWS13C029.

摘要:

细胞外基质包括胶原、层粘连蛋白和纤连蛋白等在周围神经再生中可发挥重要作用。近来,许旺细胞来源的细胞外基质复合经典的生物材料被用来模拟神经微环境,但其临床转化尚受到许旺细胞来源少、需牺牲自体神经及体外培养时间长等因素的限制。为此,我们采用容易获取、增殖速度更快的人脐带干细胞来制备细胞外基质,并对其进行形态和功能的鉴定,观察其在周围神经再生修复中的作用。研究发现,与未包被的组织培养相比,人脐带干细胞来源的细胞外基质可促进许旺细胞增殖,上调脑源性神经营养因子、胶质源性神经营养因子和血管内皮生长因子基因和蛋白的表达,并促进背根神经元的轴突的生长。说明人脐带干细胞来源的细胞外基质可促进周围神经再生,可作为组织工程神经微环境设计的基础载体。

orcid: 0000-0001-7811-5834 (Yu Wang) 0000-0001-5333-4061 (Shi-bi Lu)

关键词: 神经再生, 周围神经再生, 骨髓间充质干细胞, 细胞外基质, 许旺细胞, 背根神经节神经元, 生态位, 神经营养因子, 神经再生, 胶原, 层粘连蛋白, 纤维连接蛋白

Abstract: The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

Key words: nerve regeneration, peripheral nerve regeneration, mesenchymal stem cells, extracellular matrix, Schwann cell, dorsal root ganglion neuron, niche, neurotropic factors, collagen, laminin, fibronectin, neural regeneration