鞘内移植GMP级人类脐带间充质干细胞治疗缺血性中风的临床前安全性和有效性评估。

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Neural Regeneration Research Pub Date : 2026-03-01 Epub Date: 2024-11-13 DOI:10.4103/NRR.NRR-D-24-00683
Zejia Huang, Jiaohua Jiang, Qingxia Peng, Mengzhi Jin, Yakun Dong, Xuejia Li, Ermei Luo, Haijia Chen, Yidong Wang
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引用次数: 0

摘要

鞘内注射人脐带间充质干细胞可能是治疗中风的一种有前途的方法,但其安全性、有效性和机制仍有待阐明。本研究在大鼠大脑中动脉闭塞诱发脑卒中72小时后,通过小脑髓质贮水池注射给予良好生产规范级人脐带间充质干细胞(5×105和1×106个细胞)和生理盐水。结果表明:(1) 三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)与用生理盐水治疗的动物相比,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)随访14天和28天后,在缺血脑内发现人脐带间充质干细胞,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的神经细胞核表达量高于生理盐水组,而胶质纤维酸性蛋白和电离钙结合适配分子1的表达量则有所下降。(5)人脐带间充质干细胞治疗可增加缺血性脑卒中后CD31+微血管和双皮质素阳性细胞的数量。人脐间充质干细胞还能上调 CD31+/Ki67+ 的表达。(6)鞘内给药14天后,两组人脐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脑源性神经营养因子的浓度均显著高于生理盐水组,并持续到第28天。综上所述,这些结果表明,通过小脑髓腔注射人脐带间充质干细胞治疗大鼠缺血性脑卒中是安全有效的。其机制可能包括减轻梗死周围区域的局部炎症反应、促进神经发生和血管生成,以及增强神经营养因子的产生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202603000-00041/figure1/v/2025-06-16T082406Z/r/image-tiff 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 × 10 5 and 1 × 10 6 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 28 th 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.

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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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