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人脱落乳牙干细胞调节脊髓挫伤后早期星形胶质细胞反应。

Stem Cells from Human Exfoliated Deciduous Teeth Modulate Early Astrocyte Response after Spinal Cord Contusion.

机构信息

Post Graduate Program in Neuroscience, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2600 anexo, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil.

出版信息

Mol Neurobiol. 2019 Jan;56(1):748-760. doi: 10.1007/s12035-018-1127-4. Epub 2018 May 24.

DOI:10.1007/s12035-018-1127-4
PMID:29796991
Abstract

The transplantation of stem cells from human exfoliated deciduous teeth (SHED) has been studied as a possible treatment strategy for spinal cord injuries (SCIs) due to its potential for promoting tissue protection and functional recovery. The aim of the present study was to investigate the effects of the early transplantation of SHED on glial scar formation and astrocytic reaction after an experimental model of SCI. Wistar rats were spinalized using the NYU Impactor. Animals were randomly distributed into three groups: control (naive) (animal with no manipulation); SCI (receiving laminectomy followed by SCI and treated with vehicle), and SHED (SCI rat treated with intraspinal SHED transplantation, 1 h after SCI). In vitro investigation demonstrated that SHED were able to express mesenchymal stem cells, vimentin and S100B markers, related with neural progenitor and glial cells, respectively. The acute SHED transplantation promoted functional recovery, measured as from the first week after spinal cord contusion by Basso, Beattie, and Bresnahan scale. Twenty-four and 48 h after lesion, flow cytometry revealed a spinal cord vimentin cells increment in the SHED group. The increase of vimentin cells was confirmed by immunofluorescence. Moreover, the bioavailability of astrocytic proteins such as S100B and Kir4.1 shown to be increased in the spinal cord of SHED group, whereas there was a glial scar reduction, as indicated by ELISA and Western blot techniques. The presented results support that SHED act as a neuroprotector agent after transplantation, probably through paracrine signaling to reduce glial scar formation, inducing tissue plasticity and functional recovery.

摘要

人脱落乳牙源性干细胞(SHED)的移植已被研究作为治疗脊髓损伤(SCI)的一种可能策略,因为其具有促进组织保护和功能恢复的潜力。本研究旨在探讨早期 SHED 移植对 SCI 实验模型后神经胶质瘢痕形成和星形胶质细胞反应的影响。Wistar 大鼠采用 NYU 撞击器进行脊髓横断。动物随机分为三组:对照组(未处理的)(未进行任何操作的动物);SCI 组(接受椎板切除术,随后进行 SCI 并给予载体治疗);SHED 组(SCI 大鼠在 SCI 后 1 小时给予脊髓内 SHED 移植治疗)。体外研究表明,SHED 能够表达间充质干细胞、波形蛋白和 S100B 标志物,分别与神经祖细胞和神经胶质细胞相关。急性 SHED 移植促进了功能恢复,从脊髓挫伤后第一周开始通过 Basso、Beattie 和 Bresnahan 量表进行测量。损伤后 24 和 48 小时,流式细胞术显示 SHED 组脊髓中波形蛋白细胞增加。免疫荧光进一步证实了波形蛋白细胞的增加。此外,SHED 组脊髓中星形胶质细胞蛋白(如 S100B 和 Kir4.1)的生物利用度增加,而 ELISA 和 Western blot 技术表明神经胶质瘢痕减少。这些结果表明,SHED 在移植后作为一种神经保护剂发挥作用,可能通过旁分泌信号减少神经胶质瘢痕形成,诱导组织可塑性和功能恢复。

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SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway.SHED 来源的外泌体通过 miR-24-3p/IL-1R1/p-p38 MAPK 通路减轻小鼠眶下神经慢性压迫损伤后的三叉神经痛。
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