Extracellular Vesicle Preparation and Analysis: A State‐of‐the‐Art Review

Advanced Science, Journal Year: 2024, Volume and Issue: 11(30)

Published: June 14, 2024

Abstract In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles both health and disease states, offering promising applications diagnosis, drug delivery, therapy. However, inherent heterogeneity complex origins pose significant challenges preparation, analysis, subsequent clinical application. This review is structured provide an overview of biogenesis, composition, various sources EVs, thereby laying groundwork for a detailed discussion contemporary techniques preparation analysis. Particular focus given state‐of‐the‐art technologies that employ microfluidic non‐microfluidic platforms EV processing. Furthermore, this discourse extends into innovative approaches incorporate artificial intelligence cutting‐edge electrochemical sensors, with particular emphasis single proposes current outlines prospective avenues future research. The objective motivate researchers innovate expand methods analysis fully unlocking biomedical potential.

Language: Английский

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Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 13, 2025

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for treatment, achieving consistent clinical-grade sEV products remains significant challenge. This study aims to develop fully characterized, reproducible, batches derived from umbilical cord (UC)-MSC the treatment while assessing its efficacy safety. Initially, standardized, research-grade manufacturing protocol was established ensure production. UC-MSC-sEV characterization under non-cGMP conditions showed miRNA protein profiles, suggesting potential standardized manufacturing. In vitro studies evaluated efficacy, safety, potency sEV; animal confirmed effectiveness vitro, polarized macrophages an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating create environment in affected joints. silico sEV's immunosuppressive signature proteome analysis. mouse model, injected intra-articularly (IA) induced hyaline regeneration, validated histological μCT analyses. The unique detection signals within knee over time highlights safety profile confirming retention joint. product development involved refining, standardizing, validating processes compliance GMP standards. initial assessment via IA administration first-in-human no adverse effects after 12 month follow-up period. These results support progress this sEV-based therapy early-phase clinical trial, details which are presented discussed work. provides data on using as local OA, highlighting regenerative properties preclinical proof-of-principle application.

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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The role of the immune system in osteoarthritis: mechanisms, challenges and future directions

Nature Reviews Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Therapeutic role of hucMSC-sEV-enriched miR-13896 in cisplatin-induced acute kidney injury through M2 macrophage polarization

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 24, 2025

Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEV) have recently garnered attention as a potential therapeutic approach for kidney diseases with anti-inflammatory effects. Infiltrated macrophages play an important role in facilitating tissue regeneration. However, the intricate regulatory effects of hucMSC-sEV on during cisplatin-induced acute injury (AKI) remain unknown. In this study, we uncovered that exhibited potent anti-inflammation and effectively inhibited polarization M1 phenotype macrophages. Mechanically, miRNA sequencing analysis qRT-PCR indicated novel miRNA, named miR-13896, was enriched hucMSC-sEV. When transfected miR-13896 mimic, displayed M2 elevated levels Arg1 IL-10, while inhibitor promoted phenotype. Furthermore, firstly established repressed Tradd expression by targeting its 3' untranslated region subsequently NF-κB signaling pathway Additionally, to improve effects, were engineered through electroporation, which resulted promoting macrophages, inhibiting inflammatory factors, enhancing repair. Conclusively, our findings provide insights into mechanisms underlying AKI, also highlighting electroporation promising strategy treating AKI.

Language: Английский

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Engineering exosomes derived from TNF-α preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 11, 2024

Language: Английский

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ECM stiffness affects cargo sorting into MSC-EVs to regulate their secretion and uptake behaviors

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 21, 2024

Abstract Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered extensive attention as natural product-based nanomedicines and potential drug delivery vehicles. However, the specific mechanism for regulating MSC-EVs secretion remains unclear. Here, we demonstrate that matrix (ECM) stiffness regulates of EVs by affecting MSCs' cargo sorting mechanically. Using multi-omics analysis, found a decrease in ECM impeded vesicular transport-related proteins autophagy-related lipids into MSC-EVs, impairing their subsequent uptake macrophages. Hence, with different behaviors can be produced changing culture substrates. This study provides new insights MSC-EV biology establishes connection between from biophysical perspective, providing basis rational design biomedical materials. Graphical

Language: Английский

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Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(10), P. 1233 - 1253

Published: May 3, 2024

Due to optimised treatment strategies and the availability of new therapies during last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art cannot induce remission. Moreover, risk for flares strongly increases once anti-inflammatory therapy is tapered withdrawn, suggesting that underlying pathological processes remain active absence overt inflammation. It has evident tissues ability remember past encounters with pathogens, wounds other irritants, react more and/or persistently next occurrence. This priming tissue bears a paramount role defence from microbes, but on hand drives pathologies (the Dr Jekyll Mr Hyde aspect adaptation). Emerging evidence suggests long-lived tissue-resident cells, fibroblasts, macrophages, plasma cells memory T determine an interplay infiltrating immune lymphoid myeloid origin, systemically acting factors cytokines, extracellular vesicles antibodies. Here, we review current state science priming, focusing tissue-occupying SSc, reflect most promising options targeting maladapted response these diseases.

Language: Английский

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Engineered MSC‐sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro‐inflammatory factors. Mesenchymal stem cells‐derived small extracellular vesicles (MSC‐sEVs) have shown anti‐inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on required to facilitate translation MSC‐sEVs treatment. In this study, versatile engineered are developed targetedly clear and maintain metabolic homeostasis. Specifically, loaded with siRNA mouse double minute 2 homologue (siMDM2) modified cartilage‐targeting peptide WYRGRL‐PEG 2K ‐DSPE (WPD), named WPD‐sEVs siMDM2 . The results demonstrate modification improves cellular uptake chondrocytes, thus antiaging effects. Importantly, multifunctional enhances penetration extends joint retention time MSC‐sEVs. both post‐traumatic mice naturally aged mice, more effectively eliminates maintained matrix By using P53 phosphorylation inhibitor, essential role MDM2‐P53 pathway function verified. ex vivo cultured human explants, it confirmed that alleviates phenotype. Altogether, findings suggest promising translational potential for

Language: Английский

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Therapeutics of the future: Navigating the pitfalls of extracellular vesicles research from an osteoarthritis perspective

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(7)

Published: June 28, 2024

Abstract Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane‐bound are secreted by all cells carrying different cargos can serve both biomarkers and modifiers. Nonetheless, despite significant peak in research regarding EVs OA therapeutics, clinical implementation seems distant. In addition to scalability standardization challenges, researchers often omit focus on consider the proper tropism of vesicles, practicality relevance their source, low native therapeutic efficacy, whether they address whole. These considerations necessary better understand light been comprehensively discussed ultimately summarized this review into conceptualized framework termed nanodiamond concept. Future perspectives also discussed, alternatives presented some challenges concerns.

Language: Английский

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