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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
miRNA-146a Improves Immunomodulatory Effects of MSC-derived Exosomes in Rheumatoid Arthritis
Fataneh Tavasolian1, Ahmad Zavaran Hosseini1, Sara Soudi1
1Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Background:
Rheumatoid arthritis (RA) is a severe inflammatory joint disorder, and several studies have taken note of the probability that microRNAs (miRNAs) play an important role in RA pathogenesis. MiR-146 and miR-155 arose as primary immune response regulators. Mesenchymal stem cells (MSCs) immunomodulatory function is primarily regulated by paracrine factors, such as exosomes. Exosomes, which serve as carriers of genetic information in cell-to-cell communication, transmit miRNAs between cells and have been studied as vehicles for the delivery of therapeutic molecules.
Aims:
The current research aimed to investigate the therapeutic effect of miR-146a/miR-155 transduced mesenchymal stem cells (MSC)-derived exosomes on the immune response.
Methods:
Here, exosomes were extracted from normal MSCs with over-expressed miR-146a/miR-155; Splenocytes were isolated from collagen-induced arthritis (CIA) and control mice. Expression levels miR-146a and miR-155 were then monitored. Flow cytometry was performed to assess the impact of the exosomes on regulatory T-cell (Treg) levels. Expression of some key autoimmune response genes and their protein products, including retinoic acid-related orphan receptor (ROR)-γt, tumor necrosis factor (TNF)-α, interleukin (IL)-17, -6, -10, and transforming growth factor (TGF)-β in the Splenocytes was determined using both quantitative real-time PCR and ELISA. The results showed that miR-146a was mainly down-regulated in CIA mice. Treatment with MSC-derived exosomes and miR-146a/miR-155-transduced MSC-derived exosomes significantly altered the CIA mice Treg cell levels compared to in control mice.
Results:
Ultimately, such modulation may promote the recovery of appropriate T-cell responses in inflammatory situations such as RA.
Conclusion:
miR-146a-transduced MSC-derived exosomes also increased forkhead box P3 (Fox- P3), TGFβ and IL-10 gene expression in the CIA mice; miR-155 further increased the gene expressions of RORγt, IL-17, and IL-6 in these mice. Based on the findings here, Exosomes appears to promote the direct intracellular transfer of miRNAs between cells and to represent a possible therapeutic strategy for RA. The manipulation of MSC-derived exosomes with anti-inflammatory miRNA may increase Treg cell populations and anti-inflammatory cytokines.
Insights
Mesenchymal stem cell-derived exosomes engineered with miR-146a and miR-155 show therapeutic potential for rheumatoid arthritis (RA). These exosomes modulate immune responses by altering regulatory T-cell levels and cytokine expression, suggesting a novel treatment strategy for RA.
Area of Science:
- Immunology
- Cell Biology
- Biotechnology
Background:
- Rheumatoid arthritis (RA) is a severe inflammatory joint disorder.
- MicroRNAs (miRNAs) are implicated in RA pathogenesis.
- Mesenchymal stem cells (MSCs) and their exosomes are key in cell-to-cell communication and immune regulation.
Purpose of the Study:
- To investigate the therapeutic potential of mesenchymal stem cell (MSC)-derived exosomes engineered with miR-146a and miR-155.
- To evaluate the effect of these exosomes on immune responses in a collagen-induced arthritis (CIA) mouse model.
Main Methods:
- Exosomes were isolated from MSCs over-expressing miR-146a/miR-155.
- Splenocytes were obtained from CIA and control mice.
- Flow cytometry, quantitative real-time PCR, and ELISA were used to assess Treg levels and gene/protein expression of key immune mediators.
Main Results:
- miR-146a was downregulated in CIA mice.
- Treatment with engineered MSC-derived exosomes significantly altered regulatory T-cell (Treg) levels in CIA mice.
- Specific miRNA-transduced exosomes modulated the expression of genes like Fox-P3, TGF-β, IL-10, RORγt, IL-17, and IL-6.
Conclusions:
- MSC-derived exosomes can transfer miRNAs between cells, offering a potential therapeutic strategy for RA.
- Engineering MSC-derived exosomes with anti-inflammatory miRNAs may enhance Treg populations and anti-inflammatory cytokine production for RA treatment.
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