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

Li, Cao; Xu, Hanxin; Wang, Ge; Liu, Mei; Tian, Dean; Zhu, Yuan

doi:10.1016/j.intimp.2019.04.020

Cited by 128 publications

(94 citation statements)

References 53 publications

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“…Th1-derived IFN-γ were significantly attenuated in the gut of DSS-treated mice that received MSC-EVs. Additionally, MSC-EVs managed to increase colon concentration of immunosuppressive cytokines (IL-10 and transforming growth factor beta (TGF-β)), enabling enhanced repair and regeneration of DSS-injured epithelial cells [25]. Importantly, in vitro obtained results confirmed that MSC-EVs entered in lipopolysaccharides (LPS)-activated colon macrophages, suppressed production of inflammatory cytokines and induced generation of immunosuppressive M2 phenotype [25].…”

Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 87%

“…Several recently published studies indicated that MSC-based alleviation of colitis was mainly relied on MSC-EV-induced suppression of colon macrophages [25][26][27][28] (Figure 1). Cao and colleagues showed that MSC-EVs significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inducing polarization of colon macrophages in immunosuppressive, M2 phenotype [25]. Higher number of IL-10-producing M2 macrophages, observed in MSC-EVs-treated mice, correlated with reduced weight loss, alleviated injury of gut epithelial cells and increased colon length [25].…”

Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 99%

“…Cao and colleagues showed that MSC-EVs significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inducing polarization of colon macrophages in immunosuppressive, M2 phenotype [25]. Higher number of IL-10-producing M2 macrophages, observed in MSC-EVs-treated mice, correlated with reduced weight loss, alleviated injury of gut epithelial cells and increased colon length [25]. Concentration of macrophage-sourced inflammatory cytokines and chemokines (TNF-α, CCL-17 and CCL-24) and…”

Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 99%

See 2 more Smart Citations

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Harrell¹,

Jovičić

Djonov

et al. 2019

Cells

552

379

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There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) that regulate phenotype, function and homing of immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for the therapeutic effects of MSC-EVs in attenuation of autoimmune and inflammatory diseases. We described the disease-specific cellular targets of MSC-EVs and defined MSC-sourced molecules, which were responsible for MSC-EV-based immunosuppression. Results obtained in a large number of experimental studies revealed that both local and systemic administration of MSC-EVs efficiently suppressed detrimental immune response in inflamed tissues and promoted survival and regeneration of injured parenchymal cells. MSC-EVs-based anti-inflammatory effects were relied on the delivery of immunoregulatory miRNAs and immunomodulatory proteins in inflammatory immune cells (M1 macrophages, dendritic cells (DCs), CD4+Th1 and Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 macrophages, tolerogenic DCs and T regulatory cells. Additionally, through the delivery of mRNAs and miRNAs, MSC-EVs activated autophagy and/or inhibited apoptosis, necrosis and oxidative stress in injured hepatocytes, neurons, retinal cells, lung, gut and renal epithelial cells, promoting their survival and regeneration.

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Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 87%

Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 99%

Section: Macrophages: the Main Cellular Targets Of Msc-derived Evs Inmentioning

confidence: 99%

See 1 more Smart Citation

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Harrell¹,

Jovičić

Djonov

et al. 2019

Cells

552

379

View full text Add to dashboard Cite

show abstract

“…Speci c to IBD, there have now been several animal studies highlighting the effectiveness of MSCs and potential pathways explaining their ability to regenerate and heal colonic tissue. (18,52,53) Recently, there have also been several papers reporting the success of EVs for the treatment of DSS-induced Colitis (54,55) in a murine model. Proposed mechanisms include EVs can regulate in ammatory cells polarization and apoptosis, and involve JAK1/STAT1/STAT6/Caspase signaling pathway regulation.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

Altemus

Lightner

2020

Preprint

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Background: Mesenchymal stem cells (MSCs) are a well-established immunosuppressive agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune-responses is controversial, and its significance in the pathogenesis of IBD uncertain. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains undefined due to the lack of side-by-side comparative investigation. We herein compared MSCs and their associated EVs side-by-side using a DSS-induced colitis model. Methods: A DSS-induced colitis model was used. At Day 4, mice received adipose derived MSCs, MSC derived EVs, or placebo. Weight loss, stool consistency and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results: MSCs and EVs demonstrated equivalent immunosuppressive functions with DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Furthermore, both MSCs and EVs have an equivalent ability to inhibit inflammation in the DSS colitis model. Conclusions: These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.

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“…The total proteins, nuclear proteins, and cytoplasmic proteins of each group were extracted using the corresponding extraction kits and quantified by the total protein assay kit (BCA method). With that, whole proteins were electrophoresed in 12% polyacrylamide gels [22]. The separated proteins were transferred to polyvinylidene difluoride membranes.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Recombinant Klotho protein enhances cholesterol efflux of THP-1 macrophage-derived foam cells via suppressing Wnt/β-catenin signaling pathway

Liu

Chen

et al. 2020

BMC Cardiovasc Disord

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Background: Atherosclerosis (AS) is the basis of cardiovascular diseases, characterized by chronic inflammatory and lipid metabolism disorders. Although the anti-inflammatory effect of Klotho in AS has been clearly shown, its lipidlowering effect is unclear. In this study, we examined the effects of recombinant Klotho (Re-KL) protein on lipid accumulation in foam cells. Methods: THP-1 cells were exposed to 100 nM phorbol myristate acetate for 24 h and then to oxidized low-density lipoprotein (ox-LDL; 80 mg/mL) to induce foam cell formation. Subsequently, the foam cells were incubated with Re-KL and/or DKK1, an inhibitor of the Wnt/β-catenin pathway. Results: Oil red O staining and cholesterol intake assay revealed that the foam cell model was constructed successfully. Pretreatment of the foam cells with Re-KL decreased total cholesterol level, up-regulated the expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1), and down-regulated the expression of acyl coenzyme a-cholesterol acyltransferase 1 (ACAT1) and members of the scavenger family (SR-A1 and CD36). In addition, the expression of Wnt/β-catenin pathwayrelated proteins in foam cells was significantly decreased by the stimulus of Re-KL. Interestingly, the effect of Re-KL was similar to that of DKK1 on foam cells. Conclusions: The Re-KL-induced up-regulation of reverse cholesterol transport capacity promotes cholesterol efflux and reduces lipid accumulation by suppressing the Wnt/β-catenin pathway in foam cells.

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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

Cited by 128 publications

References 53 publications

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

Recombinant Klotho protein enhances cholesterol efflux of THP-1 macrophage-derived foam cells via suppressing Wnt/β-catenin signaling pathway

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