Dataset Information

Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells.

ABSTRACT:

Background

Adipose-derived mesenchymal stem cells (ADMSCs) can promote healing and inhibit inflammation/immune response in local tissues, while the detailed mechanism remains unknown.

Results

ADMSCs and peritoneal macrophages were collected from C57BL/6 mice. The culture medium (CM) from ADMSCs (24 hours cultured) was collected. The CM was added to the M? culture system with lipopolysaccharide (LPS) or IL-4/IL-13 or blank. And those M? cultures without adding CM were used as controls. A series of classification markers and signaling pathways for M? polarization were detected by using flow cytometry, RT-PCR, and western blotting. Furthermore, the cell viability of all the groups was detected by CCK8 assay. After CM induction in different groups, M1-M? markers and M2a-M? were decreased; however, M2b/c-M? markers increased. STAT3/SOCS3 and STAT6/IRF4 were suppressed in all 3 CM-treated groups. Moreover, the cell viability of all 3 groups which were induced by CM significantly increased as compared to that of the control groups without adding CM.

Conclusion

ADMSCs can induce nonactivated macrophage and M1-M? into M2b/c-M?. Downregulation of the STAT3 and STAT6 pathway may involve in this process. This data shows that the anti-inflammatory role of ADMSC in local tissues may be partly due to their effect on M? to M2b/c-M?.

SUBMITTER: Sun M

PROVIDER: S-EPMC6607735 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells.

Sun Meng M Sun Linxiao L Huang Chongchu C Chen Bi-Cheng BC Zhou Zhenxu Z

Journal of immunology research 20190619

<h4>Background</h4>Adipose-derived mesenchymal stem cells (ADMSCs) can promote healing and inhibit inflammation/immune response in local tissues, while the detailed mechanism remains unknown.<h4>Results</h4>ADMSCs and peritoneal macrophages were collected from C57BL/6 mice. The culture medium (CM) from ADMSCs (24 hours cultured) was collected. The CM was added to the M<i>φ</i> culture system with lipopolysaccharide (LPS) or IL-4/IL-13 or blank. And those M<i>φ</i> cultures without adding CM were ...[more]

PMID: 31321244

Similar Datasets

Project description:BACKGROUND:During the last decade, mesenchymal stem cells (MSCs) have gained much attention in the field of regenerative medicine due to their capacity to differentiate into different cell types and to promote immunosuppressive effects. However, the underlying mechanism of MSC-mediated immunoregulation is not fully understood so far. Macrophages are distinguished in classical activated, pro-inflammatory M1 and alternatively activated M2 cells, which possess different functions and transcriptional profiles with respect to inflammatory responses. As polarization is not fixed, macrophage functional plasticity might be modulated by the microenvironment allowing them to rapidly react to danger signals and maintaining tissue homeostasis. METHODS:Murine MSCs were preconditioned with IL-1ß and IFN-? to enhance their immunosuppressive capacity regarding macrophage polarization under M1- and M2a-polarizing conditions. Macrophage polarization was analyzed by real-time PCR, flow cytometry, and cytokine detection in culture supernatants. The role of MSC-derived nitric oxide (NO), prostaglandin E2 (PGE2), and IL-6 in this process has been evaluated using siRNA transfection and IL-6 receptor-deficient macrophages, respectively. RESULTS:Preconditioned, but not unprimed, MSCs secreted high levels of NO, IL-6, and PGE2. Co-culture with macrophages (M0) in the presence of M1 inducers (LPS?+?IFN-?) led to significant reduction of CD86 and iNOS protein in macrophages and diminished TNF-? secretion. Additionally, CD86 and iNOS protein expression as well as NO and IL-10 secretion were markedly increased under M2a-polarizing culture conditions (IL-4). MSC-dependent macrophage polarization did not depend on direct cell-cell contact. Co-culturing in the presence of LPS and IFN-? resulted in the upregulation of M2a, M2b, and M2c marker genes, whereas in the presence of IL-4 only M2b markers were significantly increased. In turn, IL-10-producing regulatory M2b cells significantly inhibited IFN-? expression in CD4+ T lymphocytes. Finally, we show that MSC-mediated macrophage polarization strongly depends on IL-6, whereas a minor role for NO and PGE2 was found. CONCLUSIONS:Preconditioning of MSCs highly strengthens their capacity to regulate macrophage features and to promote immunosuppression. Repression of M1 polarization during inflammation and M2b polarization under anti-inflammatory conditions strongly depend on functional IL-6 signaling in macrophages. The potential benefit of preconditioned MSCs and IL-6 should be considered for future clinical treatment.

Project description:Mesenchymal stem cells (MSCs) possess self-renewal and multipotential differentiation abilities, and they are thought to be one of the most reliable stem cell sources for a variety of cell therapies. Recently, cell therapy using MSCs has been studied as a novel therapeutic approach for cancers that show refractory progress and poor prognosis. MSCs from different tissues have different properties. However, the effect of different MSC properties on their application in anticancer therapies has not been thoroughly investigated. In this study, to characterize the anticancer therapeutic application of MSCs from different sources, we established two different kinds of human MSCs: umbilical cord blood-derived MSCs (UCB-MSCs) and adipose-tissue-derived MSCs (AT-MSCs). We used these MSCs in a coculture assay with primary glioblastoma multiforme (GBM) cells to analyze how MSCs from different sources can inhibit GBM growth. We found that UCB-MSCs inhibited GBM growth and caused apoptosis, but AT-MSCs promoted GBM growth. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling assay clearly demonstrated that UCB-MSCs promoted apoptosis of GBM via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL was expressed more highly by UCB-MSCs than by AT-MSCs. Higher mRNA expression levels of angiogenic factors (vascular endothelial growth factor, angiopoietin 1, platelet-derived growth factor, and insulin-like growth factor) and stromal-derived factor-1 (SDF-1/CXCL12) were observed in AT-MSCs, and highly vascularized tumors were developed when AT-MSCs and GBM were cotransplanted. Importantly, CXCL12 inhibited TRAIL activation of the apoptotic pathway in GBM, suggesting that AT-MSCs may support GBM development in vivo by at least two distinct mechanisms-promoting angiogenesis and inhibiting apoptosis. The opposite effects of AT-MSCs and UCB-MSCs on GBM clearly demonstrate that differences must be considered when choosing a stem cell source for safety in clinical application.

Dataset Information

Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells.

Background

Results

Conclusion

Publications

Induction of Macrophage M2b/c Polarization by Adipose Tissue-Derived Mesenchymal Stem Cells.

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