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 (12): 2306-2317.doi: 10.4103/1673-5374.284997

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

人脂肪来源和脐带来源间充质干细胞谁更适于治疗脊髓损伤

  

  • 出版日期:2020-12-15 发布日期:2020-08-05
  • 基金资助:

    广东省资助的“脑部疾病治疗关键技术”（2018B030332001）；广州卫生与医疗合作创新重大项目（201803040016-2，201604046028）;广东省科学技术计划和关键技术创新项目（2014B050504006）；中国高校学科引进人才计划（B14036）；广东省科技计划项目 （2017B090904033）

Human adipose tissue- and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

Ai-Mei Liu 1 , Bo-Li Chen 1 , Ling-Tai Yu 1 , Tao Liu 1 , Ling-Ling Shi 1 , Pan-Pan Yu 1 , Yi-Bo Qu 1, 3 , Kwok-Fai So 1, 2, 3, Li-Bing Zhou 1, 2, 3   

  1. 1 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China
    2 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong Province, China
    3 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2020-12-15 Published:2020-08-05
  • Contact: Li-Bing Zhou, PhD,tlibingzh@jnu.edu.cn; Kwok-Fai So, PhD, hrmaskf@hku.hk.
  • Supported by:
    This work was supported by Guangdong grant ‘Key Technologies for Treatment of Brain Disorders’, No. 2018B030332001 (to LBZ); Health and Medical Collaborative Innovation Major Projects of Guangzhou of China, Nos. 201803040016-2 (to LBZ), 201604046028 (to LBZ and KFS); Science & Technology Planning and Key Technology Innovation Projects of Guangdong Province of China, No. 2014B050504006 (to LBZ), Programme of Introducing Talents of Discipline to Universities of China, No. B14036 (to KFS), and Science and Technology Plan Project of Guangdong Province of China, No. 2017B090904033 (to KFS).

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摘要：

多种类型的干细胞被认为可用于治疗脊髓损伤，但是其作用机制及效果是否存在差异，早有争议。此次实验以打击法建立T10挫伤脊髓损伤大鼠模型，分别在伤后第9天损伤节段两侧注射2.5 µL人脐带来源和脂肪来源的间充质干细胞（1×105细胞/μL），并以注射间充质干细胞培养基的大鼠作为对照。结果显示，尽管移植的人脐带来源和脂肪来源的间充质干细胞无法在体内分化为神经元或神经胶质细胞，但它们均可改善脊髓损伤大鼠的运动和感觉功能。同样人脐带来源和脂肪来源的间充质干细胞也能促进脊髓损伤后神经元的存活和轴突再生，并减少了胶质瘢痕和病变空腔的形成，减少巨噬细胞的数量。(1)Bio-Plex分析显示，移植后第3天，与对照组相比，移植脂肪来源的间充质干细胞的大鼠脊髓组织中白细胞介素10表达升高，而肿瘤坏死因子α表达降低，且移植2种细胞均能下调巨噬细胞炎性蛋白3α表达；(2)而第7天时，移植2种细胞的大鼠脊髓组织中白细胞介素10和13均上调。基于iTRAQ的蛋白质组学分析表明，2种来源间充质干细胞以常规和特定方式诱导了与轴突再生、神经营养和细胞凋亡相关的多个基因的表达变化。(3)结果说明移植2种来源间充质干细胞都能通过抗炎和促轴突生长作用，促进脊髓损伤后运动和感觉功能的恢复，且作用效果相似，但是2种细胞诱导的细胞因子和基因表达存在差异。动物实验于2018年经暨南大学实验动物伦理委员会的批准（批准号20180228026），人干细胞的应用于2016年得到中国暨南大学医学院医学伦理委员会的批准（批准号2016041303）。

orcid:
0000-0002-8975-5228 (Li-Bing Zhou)
0000-0003-4039-4246 (Kwok-Fai So)

关键词: 脊髓, 干细胞, 移植, 中枢神经, 模型, 因子, 炎症, 行为

Abstract: Multiple types of stem cells have been proposed for the treatment of spinal cord injury, but their comparative information remains elusive. In this study, a rat model of T10 contusion spinal cord injury was established by the impactor method. Human umbilical cord-derived mesen- chymal stem cells (UCMSCs) or human adipose tissue-derived mesenchymal stem cells (ADMSCs) (2.5 μL/injection site, 1 × 10 5 cells/μL) was injected on rostral and caudal of the injury segment on the ninth day after injury. Rats injected with mesenchymal stem cell culture medium were used as controls. Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo, both significantly improved motor and sensory function. After spinal cord injury, UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration, decreased glial scar and lesion cavity formation, and reduced numbers of active macrophages. Bio- Plex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factor α in the ADMSC group, as well as a downregulation of macrophage inflammatory protein 3α in both UCMSC and ADMSC groups at 3 days after cell transplantation. Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation. Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration, neurotrophy, and cell apoptosis in common and specific manners. In conclusion, UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth. However, there were some differences in cytokine and gene expression induced by these two types of transplanted cells. Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University (approval No. 20180228026) on February 28, 2018, and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China (approval No. 2016041303) on April 13, 2016.

Key words: behavior, central nervous system, factor, inflammation, model, spinal cord, stem cells, transplantation