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骨髓基质细胞衍生的外泌体靶向DAB2IP以诱导小胶质细胞自噬,这是脑损伤中神经干细胞移植的一种新策略。

Bone marrow stromal cells-derived exosomes target DAB2IP to induce microglial cell autophagy, a new strategy for neural stem cell transplantation in brain injury.

作者信息

Yuan Feng-Ying, Zhang Ming-Xing, Shi Yi-Hua, Li Mei-Hui, Ou Jia-Yuan, Bai Wen-Fang, Zhang Ming-Sheng

机构信息

Department of Rehabilitation Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, P.R. China.

Department of Rehabilitation Medicine The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510600, P.R. China.

出版信息

Exp Ther Med. 2020 Sep;20(3):2752-2764. doi: 10.3892/etm.2020.9008. Epub 2020 Jul 13.

Abstract

Bone marrow stromal cells (MSCs) are a useful source of stem cells for the treatment of various brain injury diseases due to their abundant supply and fewer ethical problems compared with transplant treatment. However, the clinical application of MSCs is limited due to allograft rejection and immunosuppression in the process of MSCs transplantation. According to previous studies, microglial cell autophagy occurs following co-culture with MSCs. In the present study, exosomes were obtained from MSCs and subsequently characterized using transmission electron microscopy, atomic force microscopy and dynamic light scattering particle size analysis. The type of microRNAs (miRs) found in the exosomes was then analyzed via gene chip. The results demonstrated that microglial cell autophagy could be induced by exosomes. This mechanism was therefore investigated further via reverse transcription-quantitative PCR, western blotting and luciferase assays. These results demonstrated that exosomes from MSCs could induce microglial cell autophagy through the miR-32-mediated regulation of disabled homolog 2-interacting protein, thus providing a theoretical basis for the clinical application of miRs in MSCs.

摘要

骨髓基质细胞(MSCs)因其供应丰富且与移植治疗相比伦理问题较少,是治疗各种脑损伤疾病的有用干细胞来源。然而,由于MSCs移植过程中的同种异体排斥和免疫抑制,其临床应用受到限制。根据以往研究,小胶质细胞自噬在与MSCs共培养后会发生。在本研究中,从MSCs中获得外泌体,随后使用透射电子显微镜、原子力显微镜和动态光散射粒度分析对其进行表征。然后通过基因芯片分析外泌体中发现的微小RNA(miRs)类型。结果表明,外泌体可诱导小胶质细胞自噬。因此,通过逆转录定量PCR、蛋白质印迹和荧光素酶测定进一步研究了该机制。这些结果表明,MSCs来源的外泌体可通过miR-32介导的失能同源物2相互作用蛋白调节诱导小胶质细胞自噬,从而为miRs在MSCs中的临床应用提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a52/7401953/3e5bdeb85b3c/etm-20-03-2752-g00.jpg

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