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

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1605 - 1605

Published: Dec. 11, 2019

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) regulate phenotype, function and homing immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for therapeutic in attenuation autoimmune inflammatory diseases. We described disease-specific cellular targets defined molecules, which were MSC-EV-based immunosuppression. Results obtained a large number experimental studies revealed both local systemic administration efficiently suppressed detrimental response inflamed tissues promoted survival regeneration injured parenchymal MSC-EVs-based anti-inflammatory relied on delivery immunoregulatory miRNAs proteins cells (M1 macrophages, dendritic (DCs), CD4+Th1 Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 tolerogenic DCs T regulatory Additionally, through mRNAs miRNAs, activated autophagy and/or inhibited apoptosis, necrosis oxidative stress hepatocytes, neurons, retinal cells, lung, gut renal epithelial promoting regeneration.

Language: Английский

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Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities

Theranostics, Journal Year: 2020, Volume and Issue: 10(13), P. 5979 - 5997

Published: Jan. 1, 2020

Mesenchymal stem/stromal cells (MSCs) are important players in tissue homeostasis and regeneration owing to their immunomodulatory potential release of trophic factors that promote healing.They have been increasingly used clinical trials treat multiple conditions associated with inflammation damage such as graft versus host disease, orthopedic injuries cardiac liver diseases.Recent evidence demonstrates beneficial effects derived, at least part, from secretome.In particular, data animal models first-in-man studies indicate MSC-derived extracellular vesicles (MSC-EVs) can exert similar therapeutic origin.MSC-EVs membranous structures loaded proteins, lipids, carbohydrates nucleic acids, which play an role cell-cell communication may represent attractive alternative for cell-based therapy.In this article we summarize recent advances the use MSC-EVs repair.We highlight several isolation characterization approaches enrich EVs.We discuss our current understanding relative contribution regenerative mediated by MSCs MSC secretome.Finally challenges opportunities, come cell free therapy require repair.

Language: Английский

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Paracrine Mechanisms of Mesenchymal Stromal Cells in Angiogenesis

Stem Cells International, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 12

Published: March 9, 2020

The role of the mesenchymal stromal cell- (MSC-) derived secretome is becoming increasingly intriguing from a clinical perspective due to its ability stimulate endogenous tissue repair processes as well effective regulation immune system, mimicking therapeutic effects produced by MSCs. composite product secreted MSC in vitro (in conditioned medium) and vivo extracellular milieu), consisting protein soluble fraction (mostly growth factors cytokines) vesicular component, vesicles (EVs), which transfer proteins, lipids, genetic material. MSC-derived differs based on MSCs are isolated under specific conditions (e.g., preconditioning or priming) suggesting that applications should be tailored choosing origin priming regimen specifically correct given pathology. mediates beneficial angiogenic variety injury-related diseases. This supports current effort develop cell-free products bring both benefits (reduced immunogenicity, persistence vivo, no genotoxicity associated with long-term cell cultures) manufacturing advantages costs, availability large quantities off-the-shelf products, lower regulatory burden). In present review, we aim give comprehensive picture numerous components most common sources for use AT, BM, CB). We focus involved complex processes.

Language: Английский

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Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 27, 2020

Exosomes derived from mesenchymal stem cells (MSC-exos) have been demonstrated with great potential in the treatment of multiple human diseases including acute kidney injury (AKI) by virtue their intrinsic cargoes. However, there are major challenges low yield and lack an established biomanufacturing platform to efficiently produce MSC-exos, thereby limiting therapeutic application. Here, we aimed establish a novel strategy MSC-exos hollow fiber bioreactor-based three-dimensional (3D) culture system evaluate efficacy 3D-exosomes (3D-exos) on AKI.Mesenchymal (MSCs) were isolated fresh umbilical cord cultured two-dimensional (2D) flasks. 2 × 108 MSCs inoculated into bioreactor for 3D culture. The supernatants collected every 1 or days isolating exosomes. 2D (2D-exos) cultures characterized transmission electron microscopy, nanoparticle tracking analysis, western blotting analysis exosome markers. exosomes seeded was compared, based protein quantification. 2D-exos 3D-exos investigated murine model cisplatin-induced AKI vivo vitro.3D did not significantly change surface markers MSCs, as well morphology, size, exosomal when compared those 2D-exos. Compared conventional culture, increased total production up 19.4-fold. more concentrated harvested (15.5-fold) than 2D-exos, which led higher collection efficiency system. In vivo, both alleviated evidenced improved renal function, attenuated pathological changes tubules, reduced inflammatory factors, repressed T cell macrophage infiltration. Impressively, effective Moreover, taken tubular epithelial (TECs) efficiency, exhibiting superior anti-inflammatory effect viability TECs vitro.In summary, our findings demonstrate that provides efficient continuous has enhanced AKI.

Language: Английский

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Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases

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

Published: Sept. 27, 2021

Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials inflammatory autoimmune diseases. Emerging evidence indicates that immunomodulatory effect MSCs is primarily attributed to paracrine pathway. As one key effectors, cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm diameter play an important role cell-to-cell communication by carrying bioactive substances from parental cells. support finding MSC-EXOs obvious inhibitory toward different effector involved innate adaptive immune response. Moreover, substantial progress has made treatment diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), bowel disease (IBD). capable reproducing MSC function overcoming limitations traditional cell therapy. Therefore, using instead treat diseases appears be a promising cell-free strategy. In this review, we review current understanding discuss regulatory on its potential application

Language: Английский

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Engineered Human Adipose Stem-Cell-Derived Exosomes Loaded with miR-21-5p to Promote Diabetic Cutaneous Wound Healing

Molecular Pharmaceutics, Journal Year: 2020, Volume and Issue: 17(5), P. 1723 - 1733

Published: April 1, 2020

Diabetic wounds are a worldwide health problem causing extremely heavy public burden and require effective treatment. Optimal strategies for treating nonhealing diabetic include stem-cell-based therapy delivery of novel drug substances, such as functional microRNAs (miRNAs); however, miRNA easily degrades in the wound microenvironment. Herein, we developed human adipose stem-cell-derived exosome (hASC-exos)-based strategy to enhance its therapeutic efficacy. The miR-21-5p mimics, candidates wounds, were loaded into hASC-exos by electroporation, taking advantage natural availability biocompatibility exosomes extracellular transporting particles. engineered (E-exos) exhibited excellent effects on promoting proliferation migration keratinocytes via Wnt/β-catenin signaling vitro accelerating healing increasing re-epithelialization, collagen remodeling, angiogenesis, vessel maturation vivo. Results from this study would set fundamentals applying deliver future substances develop cell-free wound-healing treatments.

Language: Английский

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Emergence of the Stem Cell Secretome in Regenerative Engineering

Trends in biotechnology, Journal Year: 2020, Volume and Issue: 38(12), P. 1373 - 1384

Published: July 1, 2020

Language: Английский

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Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 10(7)

Published: Jan. 12, 2021

Abstract Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion angiogenesis, reduction in fibrosis. This review focuses on profiling the effects paracrine signals MSCs, commonly referred secretome, highlighting various engineering approaches tune MSC secretome. Recent advances biomaterials‐based therapeutic strategies delivery MSCs MSC‐derived secretome form extracellular vesicles are discussed, along with advantages challenges.

Language: Английский

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Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

Cell Communication and Signaling, Journal Year: 2020, Volume and Issue: 18(1)

Published: Sept. 11, 2020

Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) single stranded non-coding RNAs transcribed from DNA. miRNAs widespread in eukaryotic cells, especially mesenchymal stem cells (MSCs). MSCs used for tissue regeneration, also exert paracrine, anti-inflammatory immunomodulatory effects. However, the use of is controversial, presence or after remission a tumor, due to secretion growth factors migration ability. Instead intact MSCs, MSC-derived compartments substances could be as practical tools diagnosis, follow up, management monitoring diseases. Herein, we discuss some aspects exosomal derived progression, diagnosis treatment various Video Abstract.

Language: Английский

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Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(19), P. 7038 - 7038

Published: Sept. 24, 2020

The use of mesenchymal stem cells (MSC) for the treatment cutaneous wounds is currently enormous interest. However, broad translation cell therapies into clinical hampered by their efficacy, safety, manufacturing and cost. MSCs release a repertoire trophic factors immunomodulatory cytokines, referred to as MSC secretome, that has considerable potential cell-free therapy. In this review, we outline current status introduce secretome alternative wound repair. We discuss challenges provide insights perspectives future development well identify its therapeutic treatment.

Language: Английский

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