4.5 Article

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

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MOLECULAR BIOLOGY REPORTS
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SPRINGER
DOI: 10.1007/s11033-023-08767

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Mesenchymal stem cells; Exosomes; miR-29b; T cell differentiation; Naive CD4(+) T cells

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This study investigates the role of miR-29b in T cell differentiation reprogramming, and demonstrates that the delivery of miR-29b through adipose mesenchymal stem cell-derived exosomes alters the differentiation of CD4(+) T cells and holds promise for treating inflammatory disorders.
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 (ROR gamma t), 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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