Adipose Extracellular Vesicles in Intercellular and Inter-Organ Crosstalk in Metabolic Health and Diseases

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 25, 2021

Adipose tissue (AT) is a highly heterogeneous and dynamic organ that plays important roles in regulating energy metabolism insulin sensitivity. In addition to its classical nutrient sensing storage/dissipation, AT secretes large number of bioactive molecules (termed adipokines) participating immune responses metabolic regulation through their paracrine and/or endocrine actions. Adipose-derived extracellular vesicles (ADEVs), including exosomes, microvesicles (MVs), apoptotic bodies, have recently emerged as novel class signal messengers, mediating intercellular communications inter-organ crosstalk. AT, ADEVs derived from adipocytes, cells, mesenchymal stem endothelial cells are actively involved modulation microenvironment, adipogenesis, browing white adipose tissue, adipokine release remodeling. Furthermore, exert actions distal organs (such liver, skeletal muscle, pancreas brain) by sending genetic information (mainly the form microRNAs) target for gene expression. Here, we provide an updated summary on nature composition ADEVs, pathophysiological functions responses, whole-body sensitivity metabolism. highlight latest clinical evidence supporting aberrant production function contributor obesity-related chronic inflammation complications discuss opportunities challenges developing therapies targeting ADEVs.

Language: Английский

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Therapeutic Application of Exosomes in Inflammatory Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1144 - 1144

Published: Jan. 24, 2021

Immunomodulation is on the cusp of being an important therapy for treating many diseases, due to significant role immune system in defending human body. Although essential defense system, overactivity can result diverse sicknesses such as inflammation and autoimmune disease. Exosomes are emerging a state-of-the-art therapeutic strategy overactive system. Thus, exosomes have drawn great interest their potential clinical applications diseases associated with abnormal regulation. Hence, this review, we will discuss trends exosome research related inflammatory diseases. Possible be summarized. Finally, outlook future exosomal introduced.

Language: Английский

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Hypoxic bone marrow mesenchymal stromal cells‐derived exosomal miR ‐182‐5p promotes liver regeneration via FOXO1 ‐mediated macrophage polarization

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(10)

Published: Sept. 16, 2022

Mesenchymal stromal cells (MSCs) are attractive candidates for treating hepatic disorders given their potential to enhance liver regeneration and function. The paracrine paradigm may be involved in the mechanism of MSC-based therapy, exosomes (Exo) play an important role this activity. Hypoxia significantly improves effectiveness MSC transplantation. However, whether hypoxia preconditioned MSCs (Hp-MSCs) can regeneration, enhancement is mediated by Exo, unknown. In study, mouse bone marrow-derived (BM-MSCs) secreted Exo were injected through tail vein. We report that Hp-MSCs promote after partial hepatectomy mice exosomes. Interestingly, MSC-Exo concentrated 6 h administration mainly taken up macrophages, but not hepatocytes. Compared with normoxic (N-Exo), hypoxic (Hp-Exo) enhanced M2 macrophage polarization both vivo vitro. Microarray analysis revealed significant enrichment microRNA (miR)-182-5p Hp-Exo compared N-Exo. addition, miR-182-5p knockdown partially abolished beneficial effect Hp-Exo. Finally, Hp-MSC-derived exosomal inhibited theprotein expression forkhead box transcription factor 1 (FOXO1) which toll-like receptor 4 (TLR4) subsequently induced anti-inflammatory response. These results highlight therapeutic suggest from facilitates during modulating FOXO1/TLR4 signaling pathway.

Language: Английский

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Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 19, 2022

Abstract Purpose Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have been demonstrated to possess great potential in preclinical models. An efficient biomanufacturing platform is necessary for scale up production clinical therapeutic applications. The aim of this study investigate the differences neuro-regenerative properties MSC-derived EVs generated 2D versus 3D culture systems. Method Human bone marrow MSCs (BM-MSCs) were cultured monolayer and bioreactor isolated using ultracentrifugation followed by size concentration measurements utilizing dynamic light scattering (NanoSight) fluorescence staining (ExoView). Mouse trigeminal ganglia (TG) neurons BALB/c mice presence or absence Neuronal growth morphology monitored over 5 days immunostaining β3 tubulin. Confocal images analyzed Neurolucida software obtain density length neurites. Results NanoSight tracking analysis revealed a remarkable increase (24-fold change) obtained condition. ExoView showed significantly higher CD63, CD81, CD9 markers conditions. Furthermore, notable shift toward more heterogeneous phenotype was observed 3D-derived compared those both conditions remarkably induced neurite elongation after untreated control. (β3 tubulin) significant TG treated with 3D- 2D-derived (3301.5 μm vs. 1860.5 μm, P < 0.05). Finally, Sholl complexity neuronal ( Conclusion This highlights considerable different microenvironments, which could implications their effects potency. system seems provide preferred environment that modulates paracrine function release number enhanced biophysical functions context growth.

Language: Английский

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Advances in development of exosomes for ophthalmic therapeutics

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114899 - 114899

Published: May 24, 2023

Language: Английский

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MicroRNAs of extracellular vesicles derived from mesenchymal stromal cells alleviate inflammation in dry eye disease by targeting the IRAK1/TAB2/NF-κB pathway

The Ocular Surface, Journal Year: 2023, Volume and Issue: 28, P. 131 - 140

Published: March 27, 2023

To investigate the efficacy and mechanisms of human umbilical cord-derived MSC-derived extracellular vesicles (hucMSC-EVs) in a mouse model desiccation-induced dry eye disease (DED).hucMSC-EVs were enriched by ultracentrifugation. The DED was induced desiccating environment combined with scopolamine administration. mice divided into hucMSC-EVs group, fluorometholone (FML) PBS blank control group. Tear secretion, corneal fluorescein staining, cytokine profiles tears goblet cells, TUNEL-positive cell, CD4+ cells examined to assess therapeutic efficiency. miRNAs sequenced, top 10 used for miRNA enrichment analysis annotation. targeted DED-related signaling pathway further verified using RT‒qPCR western blotting.Treatment increased tear volume maintained integrity mice. profile group presented lower level proinflammatory cytokines than Moreover, treatment cell density inhibited apoptosis infiltration. Functional showed high correlation immunity. Among them, miR-125 b, let-7b, miR-6873 conserved between humans associated IRAK1/TAB2/NF-κB that activated DED. Furthermore, activation abnormal expression IL-4, IL-8, IL-10, IL-13, IL-17, TNF-α reversed hucMSC-EVs.hucMSCs-EVs alleviate signs, suppress inflammation restore homeostasis surface multitargeting via certain miRNAs.

Language: Английский

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Extracellular vesicles in dry eye disease and Sjogren syndrome: A systematic review on their diagnostic and therapeutic role

Survey of Ophthalmology, Journal Year: 2025, Volume and Issue: 70(3), P. 499 - 515

Published: Jan. 14, 2025

Language: Английский

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Exosomes Derived from Mouse Adipose-Derived Mesenchymal Stem Cells Alleviate Benzalkonium Chloride-Induced Mouse Dry Eye Model via Inhibiting NLRP3 Inflammasome

Ophthalmic Research, Journal Year: 2021, Volume and Issue: 65(1), P. 40 - 51

Published: Sept. 16, 2021

The objective of the study was to investigate efficacy and mechanisms mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in benzalkonium chloride (BAC)-induced dry eye model.Exosomes mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, transmission electron microscopy used characterize mADSC-Exos. An experimental model established instillation 0.2% BAC. mADSC-Exos administered following BAC treatment. positive control group treated with commercial drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, film break-up time (BUT) evaluated, histologic analysis cornea conjunctiva performed hematoxylin eosin periodic acid-Schiff staining. Apoptosis corneal epithelium detected terminal deoxynucleotidyl transferase dUTP nick-end labeling assay blotting. Levels pro-inflammatory cytokines evaluated flow cytometry, mRNA protein levels NLR family pyrin domain-containing 3 (NLRP3) pathway components assessed quantitative real-time PCR respectively.mADSC-Exos characterized as vesicles a bilayer membrane. particle size distribution peak at 134 nm. specifically expressed cluster differentiation (CD)9, CD63, CD81. treatment repaired ocular surface damage. Additionally, inhibited cell apoptosis, decreased interleukin (IL)-1β, IL-6, IL-1α, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, increased anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation upregulation caspase-1, IL-1β, IL-18 reversed mADSC-Exos.mADSC-Exos alleviate inflammation, suggesting that it is promising for eye.

Language: Английский

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Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2549 - 2549

Published: Aug. 16, 2022

Adipose-derived stem cells are a subtype of mesenchymal cell that offers the important advantage being easily obtained (in an autologous manner) from low invasive procedures, rendering high number multipotent with potential to differentiate into several cellular lineages, show immunomodulatory properties, and promote tissue regeneration by paracrine action through secretion extracellular vesicles containing trophic factors. This secretome is currently investigated as source for cell-free based regenerative therapy human tissues, which would significantly reduce involved costs, risks law regulations, allowing broader application in real clinical practice. In current article, we will review existing preclinical evidence regarding use such adipose-derived three main layers cornea: epithelium (derived surface ectoderm), stroma neural crest mesenchyme), endothelium cells).

Language: Английский

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Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4487 - 4487

Published: April 19, 2022

Therapeutic agents that are able to prevent or attenuate inflammation and ischemia-induced injury of neural retinal cells could be used for the treatment diseases. Exosomes derived from adipose tissue-sourced mesenchymal stem (AT-MSC-Exos) extracellular vesicles contain neurotrophins, immunoregulatory angio-modulatory factors secreted by their parental cells. AT-MSC-Exos enriched with bioactive molecules (microRNAs (miRNAs), enzymes, cytokines, chemokines, immunoregulatory, trophic, growth factors), alleviate promote survival injured in tissues. Due nano-sized dimension bilayer lipid envelope, easily bypass blood–brain blood–retinal barriers deliver cargo directly into target Accordingly, a large number experimental studies demonstrated beneficial effects By delivering apoptosis neurons neuritogenesis. brain, spinal cord, retinas immune cells, suppressing inflammatory properties. may act as biological mediators pro-angiogenic miRNAs endothelial enabling re-vascularization ischemic Herewith, we summarized current knowledge about molecular mechanisms which were responsible diseases, emphasizing therapeutic potential neurology ophthalmology.

Language: Английский

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