Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b
Open Access
- 24 November 2020
- journal article
- research article
- Published by Hindawi Limited in BioMed Research International
- Vol. 2020, 1-9
- https://doi.org/10.1155/2020/1621394
Abstract
The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.Funding Information
- National Research Foundation of Korea (2018R1D1A1B07050071, 2019R1C1C1007036)
This publication has 31 references indexed in Scilit:
- Exosome-delivered microRNAs modulate the inflammatory response to endotoxinNature Communications, 2015
- Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage PolarizationStem Cells International, 2015
- Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T CellsFrontiers in Immunology, 2014
- Melatonin Pretreatment Improves the Survival and Function of Transplanted Mesenchymal Stem Cells after Focal Cerebral IschemiaCell Transplantation, 2014
- Mesenchymal Stem Cells Secrete Immunologically Active ExosomesStem Cells and Development, 2014
- MicroRNAs in Immune Response and Macrophage PolarizationArteriosclerosis, Thrombosis, and Vascular Biology, 2013
- Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?Leukemia, 2011
- Malignant Tumor Formation After Transplantation of Short-Term Cultured Bone Marrow Mesenchymal Stem Cells in Experimental Myocardial Infarction and Diabetic NeuropathyCirculation Research, 2011
- Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic informationCurrent Opinion in Nephrology and Hypertension, 2010
- Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapiesExpert Opinion on Biological Therapy, 2008