Early‐Responsive Immunoregulation Therapy Improved Microenvironment for Bone Regeneration Via Engineered Extracellular Vesicles

Advanced Healthcare Materials, Год журнала: 2023, Номер 13(11)

Опубликована: Дек. 6, 2023

Abstract Overactivated inflammatory reactions hinder the bone regeneration process. Timely transformation of microenvironment from pro‐inflammatory to anti‐inflammatory after acute immune response is favorable for osteogenesis. Macrophages play an important role in inflammation. Therefore, this study adopts TIM3 high expression extracellular vesicles (EVs) with immunosuppressive function reshape early injury, mainly by targeting macrophages. These EVs can be phagocytosed macrophages, thereby increasing infiltration TIM3‐positive macrophages (TIM3 + macrophages) and M2 subtypes. The macrophage group has some characteristics secretes cytokines, such as IL‐10 TGF‐β1 regulate TIM3, which highly expressed engineered EVs, mediates release cytokines inhibiting p38/MAPK pathway promotes osseointegration activating Bmp2 promoter enhance BMP2 secretion. After evenly loading into hydrogel, continuous slow TIM3OE recruits more during stages defect repair, regulating eliminating adverse effects excessive In summary, provides a new strategy treatment refractory wounds through inflammation control.

Язык: Английский

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A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2879 - 2879

Опубликована: Март 1, 2024

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have significant impact on infant mortality long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer compelling opportunity neonatal therapy by harnessing inherent regenerative capabilities EVs. These nanoscale particles, secreted variety organisms including animals, bacteria, fungi plants, contain repertoire bioactive molecules with potential. This review aims to provide comprehensive assessment effects EVs mechanistic insights into stem cells, biological fluids non-animal sources, focus common conditions such as hypoxic–ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia necrotizing enterocolitis. summarizes evidence potential EVs, analyzes their mechanisms action discusses challenges associated implementation EV-based therapies clinical practice.

Язык: Английский

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Enrichment, Characterization, and Proteomic Profiling of Small Extracellular Vesicles Derived from Human Limbal Mesenchymal Stromal Cells and Melanocytes

Cells, Год журнала: 2024, Номер 13(7), С. 623 - 623

Опубликована: Апрель 4, 2024

Limbal epithelial progenitor cells (LEPC) rely on their niche environment for proper functionality and self-renewal. While extracellular vesicles (EV), specifically small EVs (sEV), have been proposed to support LEPC homeostasis, data sEV derived from limbal like mesenchymal stromal (LMSC) remain limited, there are no studies sEVs melanocytes (LM). In this study, we isolated conditioned media of LMSC LM using a combination tangential flow filtration size exclusion chromatography characterized them by nanoparticle tracking analysis, transmission electron microscopy, Western blot, multiplex bead arrays, quantitative mass spectrometry. The internalization was studied cytometry confocal microscopy. exhibited typical EV characteristics, including cell-specific markers such as CD90 LMSC-sEV Melan-A LM-sEV. Bioinformatics analysis the proteomic suggested significant role in matrix deposition, with LMSC-derived containing proteins involved collagen remodeling cell adhesion, whereas LM-sEV were implicated other cellular bioprocesses pigmentation development. Moreover, fluorescently labeled taken up localized perinuclear compartment. These findings provide valuable insights into complex regulating human stem niche.

Язык: Английский

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SHINE: SERS-based Hepatotoxicity detection using Inference from Nanoscale Extracellular vesicle content

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Extracellular vesicles (EV) are becoming crucial tools in liquid biopsy, diagnostics, and therapeutic applications, yet their nanoscale characterization remains challenging. In this context, the detection of drug-induced liver injury, i . e ., hepatotoxicity, through extracellular vesicle molecular content an unexplored frontier. To end, we present a label-free surface-enhanced Raman (SERS) spectroscopy approach, which provides rapid EV analysis under ten minutes requires only 1.3 microliters sample. Using hepatic cultures as model, our platform captures distinct reproducible changes response to acetaminophen-induced hepatoxicity. Our achieves exceptional accuracy with root mean squared error values low 3.80%, establishing strong correlations between spectra conventional toxicity biomarkers. Unlike previous EV-SERS studies limited identification disease markers, approach reveals drug-response signatures strongly correlated markers. These findings establish EVs dynamic reporters cellular drug responses demonstrate use SERS-based hepatotoxicity.

Язык: Английский

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In Vivo Reprogramming of Tissue‐Derived Extracellular Vesicles for Treating Chronic Tissue Injury Through Metabolic Engineering

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Extracellular vesicles (EVs) have emerged as promising therapeutics for regenerative medicine, but the efficacy of current exogenous EV-based therapies treating chronic tissue injury is still unsatisfactory. Exercise can affect skeletal muscle EV secretion and that this process regulates systemic health-promoting role exercise, suggesting fine-tuning endogenous may provide a new therapeutic avenue. Here, work reports in vivo reprogramming via metabolic engineering strategy diseases. Briefly, exercise enhanced mitochondrial metabolism production healthy muscles, EVs from muscles subjected to or (boosting biogenesis AAV-mediated muscle-specific TFAM overexpression) exerted cellular protective effects vitro. In injured therapy could reprogram patterns (reducing pathological compositions while increasing beneficial compositions) by regulating multiple cargo sorting pathways. Reprogrammed muscle-derived reach major organs tissues circulation then simultaneously attenuated multiple-tissue (e.g., kidney) kidney disease. This study highlights tissue-derived approach potential diverse

Язык: Английский

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Unveiling the functional heterogeneity of endogenous tissue extracellular vesicles in skeletal muscle through multi-omics

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 162679 - 162679

Опубликована: Апрель 1, 2025

Язык: Английский

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Mesenchymal stem cells and their extracellular vesicles: new therapies for cartilage repair

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Апрель 24, 2025

Cartilage is crucial for joints, and its damage can lead to pain functional impairment, causing financial burden patients. Due weak self-repair, cartilage injury control a research focus. naturally with age, but mechanical trauma, lifestyle factors certain genetic abnormalities increase the likelihood of symptomatic disease progression. Current treatments include pharmacological surgical interventions, these lack ability stop progression restore regeneration cartilage. Biological therapies have been evaluated show varying degrees efficacy in long-term. The mesenchymal stem cell (MSC) therapy attracts attention as it easily harvested expanded. Once thought repair via differentiation, MSCs are now known secrete extracellular vesicles (EVs) paracrinely. These EVs, rich bioactive molecules, enable communication, boost growth factor secretion, regulate synthesis degradation matrix (ECM), modulate inflammation, vital repair. However, further clinical validation still required application MSC MSC-EVs. This review highlights current state on use MSC-EVs treatment injury. It hoped that this paper will provide valuable references inspiration future researchers therapeutic studies

Язык: Английский

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Brown adipose tissue-derived extracellular vesicles regulate hepatocyte mitochondrial activity to alleviate high-fat diet-induced jawbone osteoporosis in mice

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Апрель 24, 2025

Lipid metabolic disorder (LMD) serves as a systemic driver of osteoporosis (OP), with jawbone (JOP) representing clinically significant yet underexplored complication. Current clinical treatments for JOP remain suboptimal, highlighting the need innovative approaches. The use regulators represents promising therapeutic strategy OP management. While brown adipose tissue-derived extracellular vesicles (BEV) exhibit regulatory potential, their capacity to mitigate LMD-associated remains unclear. A high-fat diet (HFD)-induced LMD mouse model was established identify phenotype through micro-computed tomography (micro-CT) and transcriptomic profiling. BEV isolation optimized using liberase enzyme-enhanced differential centrifugation, in vivo tracking confirming biodistribution. In vitro, effects on hepatocytes were assessed triglyceride (TG) content, free fatty acid (FFA) levels, mitochondrial function. additional benefits osteogenic microenvironment evaluated via AML12/MC3T3-E1 indirect co-culture under high-lipid conditions. Dual validated phenotyping, micro-CT histomorphometry analysis. Sixteen weeks HFD successfully induced typical manifestations mice. Transcriptomic sequencing revealed downregulation osteogenic-related genes concomitant upregulation lipid metabolism-associated showed exogenous predominantly accumulated liver rather than jawbone. treatment significantly reduced intracellular TG FFA content hepatocytes, while enhancing activity MC3T3-E1 cells co-culture. Mitochondrial analyses that effectively increased proportion active mitochondria, reactive oxygen species (ROS) generation rate, enhanced consumption rate (OCR) hepatocytes. Biochemical assay cage testing lower level along improved fat utilization thermogenesis BEV-treated Micro-CT immunofluorescence staining further confirm improvements mice regarding bone volume fraction, trabecular number, thickness, separation, RUNX2 expression. This study establishes crucial factor identifies BEV-mediated transferring LMD-related JOP.

Язык: Английский

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Organoid‐tissue extracellular vesicles

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Май 4, 2025

Abstract Extracellular vesicles (EVs) are lipid bilayer structures secreted by cells that act as intercellular messengers. Tissue‐derived EVs (TEVs), harvested from the tissue interstitium, directly reflect actual physiological or pathological state of microenvironment. However, difficulty in acquisition severely limits development TEVs. In contrast, organoids 3D cell clusters cultured stem cells, which have spatial and functions highly similar to source tissues. Although organoid‐derived (OEVs), isolated culture supernatants, can complex cellular interactions, they cannot microenvironment like Building on foundation TEVs OEVs, we introduce innovative concept organoid‐tissue (OTEVs), where residing organoid interstitium. Acting a communication bridge between OEVs TEVs, OTEVs accurately represent true They overcome challenges associated with limited availability inability We believe will synergize enhance understanding pathogenesis diseases, well improve their diagnosis treatment.

Язык: Английский

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Isolation and Comprehensive Analysis of Cochlear Tissue‐Derived Small Extracellular Vesicles

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Small extracellular vesicles (sEVs) act as a critical mediator in intercellular communication. Compared to sEVs derived from vitro sources, tissue‐derived can reflect the vivo signals released specific tissues more accurately. Currently, studies on role of cochlea have relied studying sources. This study evaluates three cochlear tissue digestion and sEV (CDsEV) isolation methods, first proposes that optimal approach for isolating CDsEVs using collagenase D DNase І combined with sucrose density gradient centrifugation. Furthermore, it comprehensively investigates CDsEV contents cell origins. RNA sequencing proteomics are performed analyze miRNAs proteins CDsEVs. The crucial maintaining normal auditory function. Among them, FGFR1 may mediate survival hair cells via sEVs. Finally, joint analysis single single‐cell data is utilized trace cellular origins results show different types secrete amounts CDsEVs, Kölliker's organ supporting most. findings expected enhance understanding cochlea.

Язык: Английский

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