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In vitro naive CD4+ T cell differentiation upon treatment with miR-29b-loaded exosomes from mesenchymal stem cells

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Abstract

Background

Gene regulation by microRNA (miRNA) is central in T lymphocytes differentiation processes. Here, we investigate miRNA-29b (miR-29b) roles in the reprogramming of T cell differentiation, which can be a promising therapeutic avenue for various types of inflammatory disorders such as rheumatoid arthritis and multiple sclerosis.

Methods and results

Adipose Mesenchymal Stem Cell-derived exosomes (AMSC-Exo) enriched with miR-29b were delivered into naive CD4+ T (nCD4+) cells. The expression level of important transcription factors including RAR-related orphan receptor gamma (RORγt), GATA3 binding protein (GATA3), T-box transcription factor 21, and Forkhead box P3 was determined by quantitative Real-Time PCR. Moreover, flow cytometry and Enzyme-linked Immunosorbent Assay were respectively used to measure the frequency of T regulatory cells and the levels of cytokines production (Interleukin 17, Interleukin 4, Interferon-gamma, and transforming growth factor beta. This study indicates that the transfection of miR-29b mimics into T lymphocytes through AMSC-Exo can alter the CD4+ T cells’ differentiation into other types of T cells.

Conclusions

In conclusion, AMSC-Exo-based delivery of miR-29b can be considered as a new fascinating avenue for T cell differentiation inhibition and the future treatment of several inflammatory disorders.

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Data availability

The data that support the findings of this study are available from the corresponding authors, [Hossein Ghanbarian and Seyed Mahmoud Hashemi], upon reasonable request at [hghanbarian@sbmu.ac.ir, Ghanbarian.hossein@gmail.com and smmhashemi@sbmu.ac.ir].

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Acknowledgements

We would like to thank the Iranian Stem Cell Council and Shahid Beheshti University of Medical Sciences for their valuable support.

Funding

This study was supported by the Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grant No. 18593).

Author information

Authors and Affiliations

  1. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zohreh Bolandi & Hossein Ghanbarian

  2. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zohreh Bolandi, Shahin Aghamiri, Nastaran Miyanmahaleh & Hossein Ghanbarian

  3. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi

  4. Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi & Hossein Ghanbarian

  5. Immunogenetics Research Center, Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mozhgan Abasi

  6. Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Maryam Musavi

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  1. Zohreh Bolandi
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Contributions

ZB: Investigation, Formal analysis, Methodology, Data curation, Writing—original draft, Writing—review & editing, SMH: Supervision, Project administration, Conceptualization, Writing—review & editing, MA: Investigation, Writing—original draft, SA: Investigation, Writing—original draft, NM: Writing—review & editing, MM: Investigation, HG: Conceptualization, Funding acquisition, Visualization, Project administration, Supervision, Writing—review & editing.

Corresponding authors

Correspondence to Seyed Mahmoud Hashemi or Hossein Ghanbarian.

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Informed consent was obtained from all individual participants included in the study.

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Bolandi, Z., Hashemi, S.M., Abasi, M. et al. In vitro naive CD4+ T cell differentiation upon treatment with miR-29b-loaded exosomes from mesenchymal stem cells. Mol Biol Rep 50, 9037–9046 (2023). https://doi.org/10.1007/s11033-023-08767-w

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  • DOI: https://doi.org/10.1007/s11033-023-08767-w

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