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Exosomes derived from astrocytes after oxygen-glucose deprivation promote differentiation and migration of oligodendrocyte precursor cells in vitro

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Abstract

Background

Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro.

Methods and results

Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CTexo), mild hypoxia astrocytes (O2R24exo) which were applied oxygen-glucose deprivation for 2 h and reperfusion for 24 h (OGD2hR24h) and severe hypoxia astrocytes (O4R24exo) which were applied oxygen-glucose deprivation for 4 h and reperfusion for 24 h (OGD4hR24h). Exosomes (20 µg/ml) were co-cultured with OPCs for 24 h and their proliferation, differentiation and migration were detected. The results showed that AS-Exo under severe hypoxia (O4R24exo) inhibit the proliferation of OPCs. Meanwhile, all exosomes from three groups can promote OPCs differentiation and migration. Compared to control, the expressions of MAG and MBP, markers of mature oligodendrocytes, were significantly increased in AS-Exo treatment groups. AS-Exo treatment significantly increased chemotaxis for OPCs.

Conclusions

AS-Exo improve OPCs’ differentiation and migration, whereas AS-Exo with severe hypoxic precondition suppress OPCs’ proliferation. AS-Exo may be a potential therapeutic target for myelin regeneration and repair in white matter injury or other demyelination related diseases.

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Data availability

The datasets used and analyzed during the current study are included in the manuscript submission.

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Acknowledgements

We thank Dr. Fengfei Ding for helpful discussion.

Funding

The study was supported by the National Natural Science Foundation of China (81974180, 81571113). The Innovative Scientific Research foundation of HUST (2017KFYXJJ097).

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Authors and Affiliations

  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China

    Yaping Xu, Yeye Tian, Yao Wang, Li Xu, Guini Song, Qiao Wu, Wei Wang & Minjie Xie

  2. Department of Neurology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China

    Yaping Xu

  3. Key Laboratory of Neurological Diseases of Chinese Ministry of Education, The School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Wei Wang & Minjie Xie

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  1. Yaping Xu
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Contributions

MX conceived the study and designed experiments. YX, YT, YW performed the experiments and wrote the manuscript. YX, GS, QW, LX and WW analyzed the results. All authors read and approved the final version of the manuscript.

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Correspondence to Minjie Xie.

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The authors declare that they have no competing interests.

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Animal protocols were approved by the Institutional Animal Care and Use Committee at Tongji Medical College, Huazhong University of Science and Technology.

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Supplementary Information

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11033_2021_6557_MOESM1_ESM.tif

Supplementary Fig. 1 Identification of OPCs. OPCs were identified by PDGFR-α immunostaining. Scar bar = 50 μm (TIF 10129.7 kb)

11033_2021_6557_MOESM2_ESM.tif

Supplementary Fig. 2 Apoptosis after the intervention of exosomes in OPCs. Tunel staining showed the amount of apoptosis after the intervention of exosomes in different groups was rarely. Scar bar = 100 μm (TIF 19864.8 kb)

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Xu, Y., Tian, Y., Wang, Y. et al. Exosomes derived from astrocytes after oxygen-glucose deprivation promote differentiation and migration of oligodendrocyte precursor cells in vitro. Mol Biol Rep 48, 5473–5484 (2021). https://doi.org/10.1007/s11033-021-06557-w

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  • DOI: https://doi.org/10.1007/s11033-021-06557-w

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