Dataset Information

Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a.

ABSTRACT: Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6) secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM) cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP), ?-smooth muscle actin (?-SMA), and stromal-derived factor 1 (SDF-1) expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

SUBMITTER: Cheng Q

PROVIDER: S-EPMC5733127 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a.

Cheng Qian Q Li Xin X Liu Jingru J Ye Qinmao Q Chen Yanfang Y Tan Sanqin S Liu Jing J

Stem cells international 20171127

Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6) secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM) cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) o ...[more]

PMID: 29333170

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Project description:BackgroundMyocardial ischemia-reperfusion injury is a type of myocardial ischemia that has a significant impact on patients' health. We aimed to explore the protective effect of mesenchymal stem cell-derived exosomes (MSC-EXOs) on myocardial ischemia-reperfusion injury and their specific mechanism.MethodsThe effects of MSC-EXOs on myocardial ischemia-reperfusion injury were recorded. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-6 and IL-10 in mouse myocardial tissue or culture supernatant. Co-cultured MSC-EXOs and RAW264.7 cells were used to study the effect of MSC-EXOs on the polarization of macrophages at the cellular level. The ratio of M1 and M2 macrophages were detected by flow cytometry, and RT-qPCR detected the mRNA expression levels of corresponding markers. After transfection with miR-21-5p inhibitors or mimics, flow cytometry and RT-qPCR experiments were performed to explore the specific role of MSC-EXOs in macrophage polarization.ResultsAfter injection of MSC-EXOs, the mRNA expression of M1 macrophage markers (iNOS, IL-1β, IL-6, and TNFα) in the myocardial tissue of model mice was significantly reduced (P<0.05), and the mRNA expression of M2 macrophage markers was significantly increased (P<0.05). The injection also reduced the inflammation response in the model mice (P<0.05). In the in vitro experiment, lipopolysaccharide (LPS) induced the inflammatory microenvironment. After MSC-EXOs were fixed in the cytoplasm of RAW264.7 cells, the level of IL-6 in the culture supernatant decreased (P<0.05), and the level of IL-10 increased (P<0.05). The addition of MSC-EXOs to LPS-induced RAW264.7 cells promoted their polarization toward the M2 phenotype and upregulated their marker expression levels (P<0.05). Following inhibition of miR-21-5p in MSC cells, the EXOs were collected, and it was found that MSC-EXOs that inhibited the expression of miR-21-5p promoted LPS-induced polarization of RAW264.7 cells to the M1 phenotype and upregulated inflammation in the culture supernatant. Furthermore, transfection with miR-21-5p mimics promoted the polarization of RAW264.7 cells to the M2 phenotype and reduced the level of inflammatory factors in the culture supernatant.ConclusionsMSC-EXOs promote the polarization of macrophages to the M2 phenotype via miR-21-5p, thereby reducing inflammation and promoting heart repair.

Dataset Information

Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a.

Publications

Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a.

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