中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (3): 1172-1182.doi: 10.4103/NRR.NRR-D-24-00683

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

小脑延髓池鞘内移植人脐带间充质干细胞治疗缺血性脑卒中的临床前安全性和有效性

  

  • 出版日期:2026-03-15 发布日期:2025-07-05
  • 基金资助:
    中山大学孙逸仙纪念医院逸仙医工融合专项(YXYGRH202203); 广东省科技厅重点领域研发计划“精准医学与干细胞”专项(2023B1111050003);广州市创业领军团队(201909020006)

Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke

Zejia Huang1, #, Jiaohua Jiang2, #, Qingxia Peng1 , Mengzhi Jin1 , Yakun Dong1 , Xuejia Li2 , Ermei Luo2 , Haijia Chen2, *, Yidong Wang1, 3, 4, *   

  1. 1 Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China;  2 Guangzhou SALIAI Stem Cell Science and Technology Co., Ltd., Guangzhou, Guangdong Province, China;  3 Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China;  4 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Online:2026-03-15 Published:2025-07-05
  • Contact: Haijia Chen, DBA, chenhaijia@saliai.com; Yidong Wang, MD, PhD, wangyd@mail.sysu.edu.cn or wydys@126.com.
  • Supported by:
    This work was supported by the Medicine-Engineering Interdisciplinary Project of Sun Yat-sen Memorial Hospital, China, No. YXYGRH202203 (to YW); Key-Area Research and Development Program of Guangdong Province, China, No. 2023B1111050003 (to HC); Guangzhou Science and Technology Talent Project of China, No. 201909020006 (to HC).

摘要:

既往临床前研究已显示不同移植途径人脐带间充质干细胞治疗缺血性脑卒中的潜力,然而小脑延髓池鞘内注射人脐带间充质干细胞治疗脑卒中的安全性、有效性和机制仍有待阐明。实验给予大鼠大脑中动脉阻塞模拟缺血性脑卒中72h后通过小脑髓室注射5×105、1×106剂量的良好生产规范级人脐带间充质干细胞和生理盐水。结果显示:(1) 各组大鼠的死亡率和一般状况无明显差异。各组大鼠各器官均无异常分化或肿瘤形成。(2)与生理盐水治疗的动物相比,使用人脐带间充质干细胞治疗的动物功能明显恢复,梗死体积缩小。不同剂量的人脐带间充质干细胞治疗动物之间无明显差异。(3)鞘内给药后14和 28 天,缺血大脑中发现了人脐带间充质干细胞,且阳性细胞数量随时间推移明显减少。(4)人脐带间充质干细胞组神经元特异性核蛋白的表达高于生理盐水组,而胶质纤维酸性蛋白和Iba-1 的表达则有所下降。(5)缺血性脑卒中后,人脐带间充质干细胞可增加 CD31+微血管和 DCX+细胞的数量。(6)鞘内给药后14 天,两组人脐带间充质干细胞在梗死周围区域的脑源性神经营养因子表达和脑脊液中的脑源性神经营养因子水平均显著高于生理盐水组,并持续到第 28 天。这些结果表明,脑卒中大鼠通过小脑延髓池鞘内注射人脐带间充质干细胞不仅安全而且有效,涉及的机制可能包括减轻局部炎症反应、促进神经新生和血管新生以及增强神经营养因子的产生。

https://orcid.org/0009-0000-5631-9713 (Haijia Chen); https://orcid.org/0000-0003-2228-369X (Yidong Wang)

关键词: 血管生成, 脑源性神经营养因子, 有效性, 人脐带间充质干细胞, 鞘内移植, 缺血性脑卒中, 神经细胞, 神经发生, 大鼠, 安全性

Abstract: Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke, but its safety, effectiveness, and mechanism remain to be elucidated. In this study, good manufacturing practice–grade human umbilical cord mesenchymal stem cells (5 × 105 and 1 × 106 cells) and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats. The results showed (1) no significant difference in mortality or general conditions among the three groups. There was no abnormal differentiation or tumor formation in various organs of rats in any group. (2) Compared with saline-treated animals, those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume, with no significant differences between different human umbilical cord mesenchymal stem cell doses. (3) Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up, and the number of positive cells significantly decreased over time. (4) Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group, while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased. (5) Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+ microvessels and doublecortin-positive cells after ischemic stroke. Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+ /Ki67+ . (6) At 14 days after intrathecal administration, brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day. Taken together, these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats. The mechanisms may include alleviating the local inflammatory response in the peri-infarct region, promoting neurogenesis and angiogenesis, and enhancing the production of neurotrophic factors.

Key words: angiogenesis, brain-derived neurotrophic factor, efficacy, human umbilical cord mesenchymal stem cells, intrathecal transplantation, ischemic stroke, neural cell, neurogenesis, safety