Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 7, 2023

Abstract Mesenchymal stromal/stem cells (MSCs) are widely utilized in cell therapy because of their robust immunomodulatory and regenerative properties. Their paracrine activity is one the most important features that contribute to efficacy. Recently, it has been demonstrated production various factors via extracellular vesicles, especially exosomes, governs principal efficacy MSCs after infusion experimental models. Compared themselves, MSC-derived exosomes (MSC-Exos) have provided significant advantages by efficiently decreasing unfavorable adverse effects, such as infusion-related toxicities. MSC-Exos becoming a promising cell-free therapeutic tool an increasing number clinical studies started assess effect different diseases. In this review, we summarized ongoing completed using for immunomodulation, medicine, gene delivery, beyond. Additionally, methods these with emphasis on source, isolation methods, characterization, dosage, route administration. Lastly, discussed current challenges future directions exosome utilization novel strategy.

Language: Английский

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Understanding exosomes: Part 2—Emerging leaders in regenerative medicine

Periodontology 2000, Journal Year: 2024, Volume and Issue: 94(1), P. 257 - 414

Published: Feb. 1, 2024

Abstract Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with ability to communicate other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due their be utilized as therapeutic options for a wide array diseases/conditions. Over 5000 publications currently being published yearly on this topic, number is only expected dramatically increase novel strategies continue developed. Today exosomes have been applied numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's post‐traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID‐19, hepatitis), procedures (antiaging, bone regeneration, cartilage/joint osteoarthritis, cutaneous wounds, dental dermatology/skin erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord vascular regeneration), cancer therapy (breast, colorectal, gastric osteosarcomas), immune function (allergy, autoimmune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review first its kind aimed at summarizing extensive potential broad range disorders.

Language: Английский

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Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases: a systematic review and meta-analysis of randomized controlled trials

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in treatment autoimmune rheumatic immune diseases through randomized controlled trials (RCTs). Two researchers conducted a comprehensive search Chinese English databases from their inception until Dec. 2023. The literature screening data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. A total 42 relevant RCTs, involving 2,183 participants, ultimately included this study. These RCTs encompassed four types bone diseases, namely rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic sclerosis arthritis, lupus erythematosus (SLE), inflammatory bowel disease, multiple sclerosis, primary Sjögren's syndrome (PSS). systematic review indicates that MSC may improve RA, PSS. meta-analysis reveals significantly improved symptoms patients with OA [VAS (visual analogue scale): marrow: SMD = − 0.95, 95% CI 1.55 0.36, P 0.002; umbilical cord: 1.25, 2.04 0.46, adipose tissue: -1.26, -1.99 0.52, 0.0009)], SLE [Systemic disease activity index (SLEDAI): 2.32, 3.59 1.06, 0.0003], [clinical efficacy: RR 2.02, 1.53 2.67, < 0.00001]. However, not (Ssc). Importantly, did increase incidence adverse events (OA: 1.23, 0.93 1.65, 0.15; SLE: 0.83, 0.28 2.51, 0.76; Inflammatory disease: 0.99, 0.81 1.22, 0.96; Multiple sclerosis: 1.12, 1.53, 0.50), supporting its profile across studies. findings suggest holds promise for several while highlighting areas where further research is warranted. have potential treat diseases. Moreover. appears be relatively safe could considered as viable alternative option

Language: Английский

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Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6480 - 6480

Published: June 9, 2022

Extracellular vesicles (EVs) are lipid bilayer membrane particles that play critical roles in intracellular communication through EV-encapsulated informative content, including proteins, lipids, and nucleic acids. Mesenchymal stem cells (MSCs) pluripotent with self-renewal ability derived from bone marrow, fat, umbilical cord, menstruation blood, pulp, etc., which they use to induce tissue regeneration by their direct recruitment into injured tissues, the heart, liver, lung, kidney, or secreting factors, such as vascular endothelial growth factor insulin-like factor. Recently, MSC-derived EVs have been shown regenerative effects against various diseases, partially due post-transcriptional regulation of target genes miRNAs. Furthermore, garnered attention novel drug delivery systems, because can specially encapsulate molecules. In this review, we summarize molecular mechanisms EVs.

Language: Английский

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Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases

Asian Journal of Pharmaceutical Sciences, Journal Year: 2022, Volume and Issue: 18(1), P. 100772 - 100772

Published: Dec. 31, 2022

In the inflammatory microenvironment, there are numerous exosomes secreted by immune cells (Macrophages, neutrophils, dendritic cells), mesenchymal stem (MSCs) and platelets as intercellular communicators, which participate in regulation of inflammation modulating gene expression releasing anti-inflammatory factors. Due to their good biocompatibility, accurate targeting, low toxicity immunogenicity, these able selectively deliver therapeutic drugs site through interactions between surface-antibody or modified ligand with cell surface receptors. Therefore, role exosome-based biomimetic delivery strategies diseases has attracted increasing attention. Here we review current knowledge techniques for exosome identification, isolation, modification drug loading. More importantly, highlight progress using treat chronic such rheumatoid arthritis (RA), osteoarthritis (OA), atherosclerosis (AS), bowel disease (IBD). Finally, also discuss potential challenges carriers.

Language: Английский

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Research Advances of Engineered Exosomes as Drug Delivery Carrier

ACS Omega, Journal Year: 2023, Volume and Issue: 8(46), P. 43374 - 43387

Published: Nov. 9, 2023

Exosomes are nanoscale vesicles secreted by living cells that have similar membrane composition to parental and carry a variety of proteins, lipids, nucleic acids. Therefore, exosomes certain biological activities play an important role in intercellular communication. On the basis its potential as carrier for drug delivery systems, been engineered compensate shortage natural through various engineering strategies improving efficiency, enhancing targeting tissues organs, extending circulating half-life exosomes. This review focuses on loading drugs different strategies, discussions exosome surface modification summarizes advantages disadvantages strategies. In addition, this provides overview recent applications number refractory relapsable diseases. has provide reference further research development

Language: Английский

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Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to alleviate ulcerative colitis

Theranostics, Journal Year: 2024, Volume and Issue: 14(11), P. 4278 - 4296

Published: Jan. 1, 2024

Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that strongly associated with mitochondrial damage and dysfunction as well mitophagy lacks of satisfactory treatments.Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on therapies.Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation migration abilities, their exert stronger effects than normal exosomes.However, the therapeutic function Hy-Exos in UC unknown.Methods: The inflammation model was established LPS-treated MODE-K cells, mouse by dextran sulfate sodium (DSS) administration.The HF-MSC-derived (Exos) hypoxia-preconditioned (Hy-Exos) were compared vitro vivo.Immunofluorescence staining western blotting used to explore function, fission fusion mitophagy.MiRNA sequencing analysis applied investigate differences components between Exos Hy-Exos.Results: had a better effect cells DSS-induced mice.Hy-Exos promoted colonic tight junction proteins expression, suppressed oxidative stress response, reduced UC-related injury.Hy-Exos may these via miR-214-3p-mediated inhibition PI3K/AKT/mTOR signaling pathway, maintenance dynamic stability, alleviation enhancement mitophagy. Conclusion:This study revealed vital role for suppressing progression suggested miR-214-3p potential critical target alleviating UC.

Language: Английский

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Single extracellular vesicle surface protein‐based blood assay identifies potential biomarkers for detection and screening of five cancers

Molecular Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Extracellular vesicles (EVs) and EV proteins are promising biomarkers for cancer liquid biopsy. Herein, we designed a case–control study involving 100 controls patients with esophageal, stomach, colorectal, liver, or lung to identify common type‐specific of plasma‐derived surface the five cancers. were profiled using sequencing‐based proximity barcoding assay. In this study, differentially expressed (DEPs) eight protein combinations (DEPCs) showed performance (area under curve, AUC > 0.900) in pan‐cancer identification [e.g., TENM2 (AUC = 0.982), CD36 0.974), CD36‐ITGA1 0.971)]. Our classification model could properly discriminate between DEPs 0.981) DEPCs 0.965). When distinguishing one from other four, accuracy (85–92%) was higher than that (78–84%). We validated an additional 14 controls, achieved value 0.786 0.622 DEPCs, highlighting necessity recruit larger cohort further validation. clustering EVs into subpopulations, detected cluster‐specific highly immune‐related tissues. context colorectal cancer, identified heterogeneous clusters enriched patients, correlating tumor initiation progression. These findings provide epidemiological molecular evidence clinical application prediction, while also illuminating their functional roles physiopathology.

Language: Английский

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Stem Cell-Derived Exosomes: An Advanced Horizon to Cancer Regenerative Medicine

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(4), P. 2128 - 2139

Published: April 3, 2024

Cancer research has made significant progress in recent years, and extracellular vesicles (EVs) based cancer investigation reveals several facts about cancer. Exosomes are a subpopulation of EVs. In the present decade, exosomes is mostly highlighted for theranostic research. Tumor cell derived (TEXs) promote but there multiple sources that can be used as therapeutic agents (plant exosomes, stem cell-derived modified or synthetic exosomes). Stem cells regenerative medicine faces numerous challenges, such tumor development, cellular reprogramming etc., therefore addressing these complications becomes essential. serves an answer to problems offers better solution. Global indicates also play dual role system by either inhibiting promoting Modified which genetically engineered surface increase efficacy properties considered target above concerns. However, difficulties associated with include variations heterogenity, isolation protocols, large scale production, have managed effectively. this review, we explore biogenesis, exosome sources, drug delivery, clinical trial related challenges domain future orientation. This article may encourage researchers develop effective affordable

Language: Английский

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Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 15, 2024

Abstract In recent decades, emerging data have highlighted the critical role of extracellular vesicles (EVs), especially (exosomes) Exos, in progression and development several cancer types. These nano-sized are released by different cell lineages within niche maintain a suitable platform for interchange various signaling molecules paracrine manner. Based on studies, Exos can transfer oncogenic factors to other cells, alter activity immune tumor microenvironment, leading expansion cells metastasis remote sites. It has been indicated that cell-to-cell crosstalk is so complicated wide array involved this process. How which mechanisms regulate behavior non-cancer at center debate. Here, we scrutinize molecular parenchyma. Besides, tumoricidal properties from stem (SC) types discussed detail.

Language: Английский

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