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毛囊干细胞经鼻腔移植治疗缺血性脑卒中大鼠模型的研究

Therapeutic potential of hair follicle-derived stem cell intranasal transplantation in a rat model of ischemic stroke.

机构信息

Department of Basic Sciences, Faculty of Veterinary Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran.

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

BMC Neurosci. 2022 Jul 25;23(1):47. doi: 10.1186/s12868-022-00732-w.

Abstract

BACKGROUND

Stem cell-based therapy has received considerable attention as a potential candidate in the treatment of ischemic stroke; however, employing an appropriate type of stem cells and an effective delivery route are still challenging. In the present study, we investigated the therapeutic effect of safe, noninvasive, and brain-targeted intranasal administration of hair follicle-derived stem cells (HFSCs) in a rat model of ischemic stroke.

METHODS

Stem cells were obtained from the adult rat hair follicles. In experiment 1, stroke was induced by 30 min middle cerebral artery occlusion (MCAO) and stem cells were intranasally transplanted immediately after ischemia. In experiment 2, stroke was induced by 120 min MCAO and stem cells were administered 24 h after cerebral ischemia. In all experimental groups, neurological performance, short-term spatial working memory and infarct volume were assessed. Moreover, relative expression of major trophic factors in the striatum and cortex was evaluated by the quantitative PCR technique. The end point of experiment 1 was day 3 and the end point of experiment 2 was day 15.

RESULTS

In both experiments, intranasal administration of HFSCs improved functional performance and decreased infarct volume compared to the MCAO rats. Furthermore, NeuN and VEGF expression were higher in the transplanted group and stem cell therapy partially prevented BDNF and neurotrophin-3 over-expression induced by cerebral ischemia.

CONCLUSIONS

These findings highlight the curative potential of HFSCs following intranasal transplantation in a rat model of ischemic stroke.

摘要

背景

干细胞疗法作为缺血性中风治疗的潜在候选物受到了广泛关注;然而,选择合适的干细胞类型和有效的递送途径仍然具有挑战性。在本研究中,我们研究了安全、非侵入性、靶向大脑的鼻腔内给予毛囊干细胞(HFSCs)在缺血性中风大鼠模型中的治疗效果。

方法

从成年大鼠毛囊中获得干细胞。在实验 1 中,通过 30 分钟大脑中动脉闭塞(MCAO)诱导中风,并在缺血后立即通过鼻腔内移植干细胞。在实验 2 中,通过 120 分钟 MCAO 诱导中风,并在脑缺血后 24 小时给予干细胞。在所有实验组中,评估了神经功能表现、短期空间工作记忆和梗死体积。此外,通过定量 PCR 技术评估纹状体和皮质中主要营养因子的相对表达。实验 1 的终点为第 3 天,实验 2 的终点为第 15 天。

结果

在两项实验中,与 MCAO 大鼠相比,鼻腔内给予 HFSCs 可改善功能表现并减少梗死体积。此外,移植组的 NeuN 和 VEGF 表达更高,且干细胞治疗部分预防了脑缺血引起的 BDNF 和神经营养因子-3 过表达。

结论

这些发现强调了 HFSCs 经鼻腔内移植在缺血性中风大鼠模型中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/add1/9316709/6c9bb378f477/12868_2022_732_Fig1_HTML.jpg

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