Preconditioning of canine adipose tissue-derived mesenchymal stem cells with deferoxamine potentiates anti-inflammatory effects by directing/reprogramming M2 macrophage polarization

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.

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Surgical meshes coated with mesenchymal stem cells provide an anti-inflammatory environment by a M2 macrophage polarization

Acta Biomaterialia ◽

10.1016/j.actbio.2015.11.057 ◽

2016 ◽

Vol 31 ◽

pp. 221-230 ◽

Cited By ~ 17

Author(s):

Rebeca Blázquez ◽

Francisco Miguel Sánchez-Margallo ◽

Verónica Álvarez ◽

Alejandra Usón ◽

Javier G. Casado

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Surgical Meshes ◽

M2 Macrophage Polarization ◽

Anti Inflammatory

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Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury

International Immunopharmacology ◽

10.1016/j.intimp.2021.107835 ◽

2021 ◽

Vol 98 ◽

pp. 107835

Author(s):

Jiakun Tian ◽

Xiaoqian Cui ◽

Jian Sun ◽

Jingxiao Zhang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Adipose Mesenchymal Stem Cells ◽

M2 Macrophage Polarization ◽

Exosomal Microrna

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Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization

International Immunopharmacology ◽

10.1016/j.intimp.2019.04.020 ◽

2019 ◽

Vol 72 ◽

pp. 264-274 ◽

Cited By ~ 17

Author(s):

Li Cao ◽

Hanxin Xu ◽

Ge Wang ◽

Mei Liu ◽

Dean Tian ◽

...

Keyword(s):

Ulcerative Colitis ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Sodium Sulfate ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Marrow Mesenchymal Stem Cells ◽

M2 Macrophage Polarization

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MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against renal injury in diabetic nephropathy through facilitating M2 macrophage polarization by targeting TRAF6

10.21203/rs.3.rs-871704/v1 ◽

2021 ◽

Author(s):

Yaqi Zhang ◽

Xi Le ◽

Shuo Zheng ◽

Ke Zhang ◽

Jing He ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Renal Function ◽

Diabetic Nephropathy ◽

High Throughput ◽

Renal Injury ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Human Umbilical Cord ◽

M2 Macrophage Polarization

Abstract Background Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease, but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation. Methods This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell line and UC-MSCs-derived conditional medium was used to assess the involvement of macrophage polarization signaling. Results UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an antiinflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting TRAF6-STAT1 signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement. Conclusions Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. It will pave the way for the use of UC-MSCs for therapeutic delivery of miRNAs targeted at kidney diseases.

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Human umbilical cord mesenchymal stem cells derived Exosomes attenuate injury of myocardial infarction by miR-24-3p-promoted M2 macrophage polarization

10.21203/rs.3.rs-406792/v1 ◽

2021 ◽

Author(s):

Feng Zhu ◽

Yihuan Chen ◽

Jingjing Li ◽

Ziying Yang ◽

Yang Lin ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Macrophage Polarization ◽

M2 Macrophage ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Pathway Activation ◽

M2 Macrophage Polarization

Abstract Background- Exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs-Exo) were recommended as ideal substitutes for cell-free cardiac regenerative medicine, which had presented encouraging effects in regulating inflammation and attenuating myocardial injury. The phenotype of macrophages resident in myocardium were regulated dynamically in response to environmental cues, which may either protect against injury or promote maladaptive remodeling. However, the underlying mechanisms about UMSCs-Exo regulating macrophage polarization are still not well understood. Herein, we aimed to explore the effects of UMSCs-Exo on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). Methods and Results- Exosomes were isolated from the supernatant of human umbilical cord mesenchymal stem cells (UMSCs) and transplanted by intramyocardial injection after MI. Our results showed that UMSCs-Exo improved cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. After depletion of macrophages with clodronate liposomes, the therapeutic effects of UMSCs-Exo were disrupted. Administrated with UMSC-Exo, macrophages are inclined to polarize towards M2 phenotype in inflammatory environment in vitro. The results of RNA-sequencing indicated Plcb3 was a key gene concerned in UMSCs-Exo facilitated M2 macrophage polarization. Further bioinformatics analysis revealed exosomal miR-24-3p as a potential effector mediated Plcb3 down regulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhanced M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in inflammatory environment. Furthermore, diminishing miR-24-3p expression in UMSCs-Exo attenuated the effects of UMSCs-Exo on M2 macrophage polarization. Conclusions- Our study demonstrated that macrophages, as important inflammatory regulators, participated in UMSCs-Exo mediated myocardial repair after MI. And the therapeutical effects were at least partially carried out by UMSCs-Exo promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanically, exosomal miR-24-3p inhibits the expression of Plcb3 and NF-κB pathway activation to promote M2 macrophage polarization.

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Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

International Journal of Molecular Sciences ◽

10.3390/ijms22031375 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1375

Author(s):

María Carmen Carceller ◽

María Isabel Guillén ◽

María Luisa Gil ◽

María José Alcaraz

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Extracellular Vesicles ◽

Nuclear Factor Κb ◽

Peritoneal Macrophages ◽

Toll Like Receptor 4 ◽

Anti Inflammatory ◽

Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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