中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (2): 354-361.doi: 10.4103/1673-5374.317985

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

人脐带间充质干细胞移植治疗创伤性脑损伤的临床前研究：基于免疫原性和致瘤性的安全性评价

  

  • 出版日期:2022-02-15 发布日期:2021-10-08

Pre-clinical study of human umbilical cord mesenchymal stem cell transplantation for the treatment of traumatic brain injury: safety evaluation from immunogenic and oncogenic perspectives

Gang Wang1, 2, #, Hua-Ling Wu3, #, Yue-Ping Liu1, 2, #, De-Qi Yan4, Zi-Lin Yuan1, 2, Li Chen1, 2, Qian Yang1, 2, Yu-Song Gao4, Bo Diao1, 2, *   

  1. 1Basic Medical Laboratory, General Hospital of the Central Theater Command, Wuhan, Hubei Province, China; 2Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei Province, China; 3Department of Clinical Laboratory, The Third People’s Hospital of Yongzhou, Yongzhou, Hunan Province, China; 4Department of Neurosurgery, 990th Hospital of Joint Logistic Support Troops of PLA, Zhumadian, Henan Province, China
  • Online:2022-02-15 Published:2021-10-08
  • Contact: Bo Diao, MD, dpitao@163.com.
  • Supported by:
    The work was supported by the General Project of Hubei Health Committee of China, No. WJ2019M263 (to GW).

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摘要：

干细胞似乎是治疗创伤性脑损伤的一种潜在策略，但是在其临床应用前需进行动物实验以评估人脐带间充质干细胞移植的安全性，尤其是免疫原性和致瘤性。实验首先从人羊膜和脐带血管组织中获取人脐带间充质干细胞，然后利用控制性皮质撞击法建立创伤性脑损伤大鼠模型，从损伤后第3天起，脑立体定位注射10μL 5×106/mL人脐带间充质干细胞或从第3天起，连续3d每天一次通过尾静脉注射500μL 1×106/mL人脐带间充质干细胞。结果显示，人脐带间充质干细胞移植能够持续降低创伤性脑损伤大鼠血清中促炎因子表达水平并提升抗炎细胞因子表达水平，表现出良好的免疫调节功能；移植的人脐带间充质干细胞在肝、肺和脑损伤部位均有分布，在移植12个月后也没有在上述器官发现异常增生和致瘤性病变；移植的人脐带间充质干细胞在体内增殖活性较低，后期逐渐凋亡并被代谢。表明人脐带间充质干细胞移植治疗创伤性脑损伤具有良好的安全性。此外，人脐带间充质干细胞具有良好的免疫调节功能，有助于预防和改善创伤性脑损伤后因炎症因子急剧释放而导致的继发性脑损伤。实验于2016年11月1日经解放军武汉总医院伦理委员会批准（批准号20160054）。

https://orcid.org/0000-0002-2209-6061 (Bo Diao)

关键词: font-family:宋体, ">创伤性脑损伤, 间充质干细胞, 细胞移植, 安全性, 免疫原性, 致瘤性, 炎症, 免疫调节

Abstract: Stem cell therapy is a promising strategy for the treatment of traumatic brain injury (TBI). However, animal experiments are needed to evaluate safety; in particular, to examine the immunogenicity and tumorigenicity of human umbilical cord mesenchymal stem cells (huMSCs) before clinical application. In this study, huMSCs were harvested from human amniotic membrane and umbilical cord vascular tissue. A rat model of TBI was established using the controlled cortical impact method. Starting from the third day after injury, the rats were injected with 10 μL of 5 × 106/mL huMSCs by cerebral stereotaxis or with 500 μL of 1 × 106/mL huMSCs via the tail vein for 3 successive days. huMSC transplantation decreased the serum levels of proinflammatory cytokines in rats with TBI and increased the serum levels of anti-inflammatory cytokines, thereby exhibiting good immunoregulatory function. The transplanted huMSCs were distributed in the liver, lung and brain injury sites. No abnormal proliferation or tumorigenesis was found in these organs up to 12 months after transplantation. The transplanted huMSCs negligibly proliferated in vivo, and apoptosis was gradually observed at later stages. These findings suggest that huMSC transplantation for the treatment of traumatic brain injury displays good safety. In addition, huMSCs exhibit good immunoregulatory function, which can help prevent and reduce secondary brain injury caused by the rapid release of inflammatory factors after TBI. This study was approved by the Ethics Committee of Wuhan General Hospital of PLA (approval No. 20160054) on November 1, 2016.

Key words: cell transplantation, immune regulation, inflammation, mesenchymal stem cells, safety evaluation, immunogenicity, traumatic brain injury, tumorigenesis

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