Bone marrow macrophage M2 polarization and adipose‐derived stem cells osteogenic differentiation synergistically promote rehabilitation of bone damage

Li, Yiyang; Kong, Ning; Li, Zhe; Tian, Run; Liu, Xiaohui; Liu, Guanzhi; Wang, Kunzheng; Yang, Pei

doi:10.1002/jcb.29297

Cited by 26 publications

(30 citation statements)

References 45 publications

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“…Increasing evidence indicated that MSCs could develop immunosuppressive properties by regulating the phenotypes and activities of innate and adaptive immune cells. In the microenvironment regulated by MSCs, T cells transformed into a tolerant Treg phenotype; macrophages transformed into an immunoregulatory M2-macrophages phenotype; NK cells transformed into non-free functional status, and MSCs could suppress the production of immunoglobulins and increase the production of regulatory B cells (Bregs) (31)(32)(33)(34). Cell-tocell contact dependent and independent ways to develop its' immunosuppression by blocking immune cell differentiation and cell cycle are described as the exact mechanisms (4,5,9,17).…”

Section: The Immunomodulatory Ability Of Stem Cellsmentioning

confidence: 99%

“…Ligand type Target cells Disease or microenvironment References ICAM-1 LFA-1 Macrophage T cells Microglia DC cells Neutrophils T cell Ag receptor' activated CD3+ pan-T cells activation (41) Autoimmune thyroiditis (6) Bony defect (32) Improve cerebral infarction (3,48) Alzheimer's disease (15) Multiple sclerosis (49) Ischemic stroke (50) Galectin-9 (sGal-9) TIM-3 T cells DC cells Macrophage αCD28/OKT3-activated PBMC (60) Hepatocyte chronic infection caused by HCV (63) Chronic HCV infection and promote immunotolerance (64) GVHD (16,45,65) Autoimmune diabetes in NOD mice (66) Autoimmune cholangitis (67) Multiple sclerosis (68) PHA activated PBMC (69) Normal PBMC or abortion-PBMC 70LPS-Induced Preeclampsia-Like Impairment (72) LPS-induced M1-macrophage (73) Experimental hypersensitivity pneumonitis (71) Galectin-1 sGal-1 T cells PHA-stimulated PBMC (76) Ovalbumin-induced DTH model (76) Free-serum in α-MEM essential medium (80) Mice injected orthotopically with breast carcinoma cells or subcutaneously with melanoma cells (81,83) Galectin-3 sGal-3 T cells Induced medium which contained L-DMEM, 5% FBS, VEGF (10 ng/mL), and bFGF (2 ng/mL)…”

Section: Receptor Typementioning

confidence: 99%

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Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Liu

Zhou

et al. 2020

Front. Immunol.

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In the past decade, mesenchymal stem cells (MSCs) tend to exhibit inherent tropism for refractory inflammatory diseases and engineered MSCs have appeared on the market as therapeutic agents. Recently, engineered MSCs target to cell surface molecules on immune cells has been a new strategy to improve MSC applications. In this review, we discuss the roles of multiple receptors (ICAM-1, Gal-9, PD-L1, TIGIT, CD200, and CXCR4) in the process of MSCs' immunosuppressive properties. Furthermore, we discuss the principles and strategies for developing receptor-regulated MSCs and their mechanisms of action and the challenges of using MSCs as immunosuppressive therapies.

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Section: The Immunomodulatory Ability Of Stem Cellsmentioning

confidence: 99%

Section: Receptor Typementioning

confidence: 99%

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Liu

Zhou

et al. 2020

Front. Immunol.

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“…Macrophage is a critical component of the immune system, diffusely distributed in the body, expressing various bioactive substances, receptors and enzymes [5]. M2 macrophage ordinarily triggers cell proliferation, extracellular matrix synthesis and tissue remodeling [6]. A study has reported that M2 phenotype macrophages secret transforming growth factor-β1 to promote the migration and stemness of glioma cells [7].…”

Section: Introductionmentioning

confidence: 99%

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Yang

Wang

et al. 2020

Cancer Cell Int

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Background: Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods: Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was cocultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8 + T cells were isolated. CD8 + T cells were co-cultured with U87 cells to detect the CD8 + T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8 + T cells was detected. Results: PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8 + T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8 + T cells in glioma mice.

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“…To effectively repair bone defects duo to tumour resection, bone biomaterials should provide appropriate media for angiogenesis and osteogenesis (29). In vitro, M2 macrophages directly regulate osteogenic differentiation of bone marrow mesenchymal stem cells (30,31). The mechanism may be due to proregenerative cytokines produced by M2 macrophages, such as TGF-β, VEGF, Ang-1 and IFG-1 (32).…”

Section: Introductionmentioning

confidence: 99%

Graphene-Modified CePO4 Nanorods Effectively Treat Breast Cancer-Induced Bone Metastases and Regulate Macrophage Polarization to Improve Osteo-Inductive Ability

Liu

et al. 2020

Preprint

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Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion and local bone defects.Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through CCK8 experiment, staining of living dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verified whether bioscaffold materials regulated the polarization of macrophages, and we use ALP staining, alizarin red staining and PCR to verify whether the bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration.Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffolds, which has the following characteristics such as photothermal therapy to kill tumors, macrophage polarization promotes blood vessel formation and induces bone formation. The CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote the M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated BMP-2/Smad signaling pathway that facilitated bone tissue regeneration.Conclusion the multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

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Bone marrow macrophage M2 polarization and adipose‐derived stem cells osteogenic differentiation synergistically promote rehabilitation of bone damage

Cited by 26 publications

References 45 publications

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors

M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3

Graphene-Modified CePO4 Nanorods Effectively Treat Breast Cancer-Induced Bone Metastases and Regulate Macrophage Polarization to Improve Osteo-Inductive Ability

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