Unraveling The Effects of DICER1 Overexpression on Immune-Related Genes Expression in Mesenchymal Stromal/Stem Cells: Insights for Therapeutic Applications

Hamid Reza Bidkhori; Moein Farshchian; Halimeh Hasanzadeh; Reza Jafarzadeh Esfehani; Reihaneh Alsadat Mahmoudian; Mahdi Moradi Marjaneh; Houshang Rafatpanah

doi:10.22074/cellj.2023.1988987.1221

Cell Journal (Oct 2023)

Unraveling The Effects of DICER1 Overexpression on Immune-Related Genes Expression in Mesenchymal Stromal/Stem Cells: Insights for Therapeutic Applications

Hamid Reza Bidkhori,
Moein Farshchian,
Halimeh Hasanzadeh,
Reza Jafarzadeh Esfehani,
Reihaneh Alsadat Mahmoudian,
Mahdi Moradi Marjaneh,
Houshang Rafatpanah

Affiliations

Hamid Reza Bidkhori: Immunology Research Centre, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran
Moein Farshchian: Stem Cells and Regenerative Medicine Department, Academic Center for Education, Culture, and Research (ACECR) - Khorasan Razavi, Iran
Halimeh Hasanzadeh: Stem Cells and Regenerative Medicine Department, Academic Center for Education, Culture, and Research (ACECR) - Khorasan Razavi, Iran
Reza Jafarzadeh Esfehani: Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR) - Khorasan Razavi, Iran
Reihaneh Alsadat Mahmoudian: Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Mahdi Moradi Marjaneh: Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
Houshang Rafatpanah: Immunology Research Centre, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran

DOI: https://doi.org/10.22074/cellj.2023.1988987.1221
Journal volume & issue: Vol. 25, no. 10
pp. 696 – 705

Abstract

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Objective: The immunoregulatory properties of mesenchymal stromal/stem cells (MSCs) bring a promise for thetreatment of inflammatory diseases. However, their ability to suppress the immune system is unstable. To enhance theireffectiveness against immune responses, it may be necessary to manipulate MSCs. Although some dsRNA transcriptscome from invading viruses, the majority of dsRNA has an endogenous origin and is known as endo-siRNA. DICER1 isa ribonuclease protein that can generate small RNAs to modulate gene expression at the post-transcriptional level. Weaimed to evaluate the expression of several immune-related genes at mRNA and protein levels in MSCs overexpressingDICER1 exogenously.Materials and Methods: In this comparative transcriptomic experimental study, the adipose-derived MSCs (Ad-MSCs) weretransfected using the pCAGGS-Flag-hsDicer vector for the DICER1 overexpression. Following the RNA extraction,mRNA expression level of DICER1 and several inflammatory cytokines were examined. We performed a relativereal-time polymerase chain reaction (PCR) assay and transcriptome analysis between two groups including DICER1-transfected MSCs and control MSCs. Moreover, media from the transfected MSCs were evaluated for various interferonresponse factors by ELISA.Results: The overexpression of DICER1 is associated with a significant increase in the mRNA expression level ofCOX-2, DDX-58, IFIH1, MYD88, RNase L, TLR3/4, and TDO2 genes and a downregulation of the TSG-6 gene inMSCs. Moreover, the expression levels of IL-1, 6, 8, 17, 18, CCL2, INF-γ, TGF-β, and TNF-α were higher in theDICER1-transfected MSCs group.Conclusion: It seems that the ectopic expression of DICER1 in Ad-MSCs is linked to alterations in the expression levelof immune-related genes. It is suggested that the manipulation of immune-related pathways in MSCs via the Dicer1overexpression could facilitate the development of MSCs with distinct immunoregulatory phenotypes.

Published in Cell Journal

ISSN: 2228-5806 (Print); 2228-5814 (Online)
Publisher: Royan Institute (ACECR), Tehran
Country of publisher: Iran, Islamic Republic of
LCC subjects: Medicine; Science
Website: http://celljournal.org/

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