Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases

Journal of Extracellular Vesicles, Год журнала: 2023, Номер 12(2)

Опубликована: Фев. 1, 2023

Abstract Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular interorgan communication. The capability to modulate their stability, tissue‐specific targeting cargo render EVs as promising nanotherapeutics for treating heart, lung, blood sleep (HLBS) diseases. However, current limitations large‐scale manufacturing of therapeutic‐grade EVs, knowledge gaps EV biogenesis heterogeneity pose significant challenges clinical application diagnostics or therapeutics HLBS To address these challenges, a strategic workshop with multidisciplinary experts biology U.S. Food Drug Administration (USFDA) officials was convened by the National Heart, Lung Blood Institute. presentations discussions were focused on summarizing state science technology engineering therapeutic diseases, identifying critical regulatory suggesting potential solutions promulgate translation clinic. Benchmarks meet quality attributes set USFDA other cell‐based discussed. Development novel strategies approaches scaling‐up production control/quality analysis (QC/QA) EV‐based recognized necessary milestones future investigations.

Язык: Английский

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Extracellular vesicles as human therapeutics: A scoping review of the literature

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(5)

Опубликована: Май 1, 2024

Abstract Extracellular vesicles (EVs) are released by all cells and contribute to cell‐to‐cell communication. The capacity of EVs target specific efficiently deliver a composite profile functional molecules have led researchers around the world hypothesize their potential as therapeutics. While studies EV treatment in animal models numerous, actual clinical benefit humans has more slowly started be tested. In this scoping review, we searched PubMed other databases up 31 December 2023 and, starting from 13,567 records, selected 40 pertinent published testing therapeutics humans. analysis those shows that they small pilot trials with large heterogeneity terms administration route disease. Moreover, absence placebo control most studies, predominant local application formulations inconsistent dose metric still impede comparison across firm conclusions about safety efficacy. On hand, recording some promising outcomes strongly calls out for well‐designed larger test an alternative approach treat human diseases no or few therapeutic options.

Язык: Английский

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Exosomal circRNAs: Novel biomarkers and therapeutic targets for urinary tumors

Cancer Letters, Год журнала: 2024, Номер 588, С. 216759 - 216759

Опубликована: Фев. 28, 2024

Язык: Английский

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Plant and mammalian-derived extracellular vesicles: a new therapeutic approach for the future

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Сен. 13, 2023

Background: In recent years, extracellular vesicles have been recognized as important mediators of intercellular communication through the transfer active biomolecules (proteins, lipids, and nucleic acids) across plant animal kingdoms considerable roles in several physiological pathological mechanisms, showing great promise new therapeutic strategies for a variety pathologies. Methods: this study, we carefully reviewed numerous articles published over last few decades on general knowledge vesicles, their application therapy various pathologies, prospects an approach future. Results: The discovery characterization (EVs) diverse origins biogenesis altered current paradigm communication, opening up diagnostic perspectives. Research into these EVs released by mammalian cells has revealed involvement number such embryonic development, immune response, tissue regeneration, cancer. They are also being studied potential biomarkers disease diagnosis vectors drug delivery. Conclusion: Nanovesicles represent powerful tools bioactive molecules. Their molecular composition functions can vary according to origin (plant mammalian), so formation, composition, biological open way applications which is arousing growing interest scientific community. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03608631.

Язык: Английский

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Strategies for Engineering of Extracellular Vesicles

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13247 - 13247

Опубликована: Авг. 26, 2023

Extracellular vesicles (EVs) are membrane released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, organelles within human body. gained a particular interest from cancer biology scientists because their role in modulation tumor microenvironment delivering bioactive molecules. In this respect, represent an attractive therapeutic target means for drug delivery. The advantages include biocompatibility, small size, low immunogenicity. However, there several limitations that restrict widespread use therapy, namely, specificity payload capacity. Thus, order to enhance efficacy delivery specificity, surface composition should be modified accordingly. review, we describe various approaches engineering EVs, further discuss disadvantages promote application clinical practice.

Язык: Английский

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Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine

Cell Proliferation, Год журнала: 2024, Номер 57(8)

Опубликована: Март 10, 2024

Abstract Mesenchymal stem cell‐derived exosomes (MSC‐Exo) offer promising therapeutic potential for various refractory diseases, presenting a novel strategy. However, their clinical application encounters several obstacles, including low natural secretion, uncontrolled biological functions and inherent heterogeneity. On the one hand, physical stimuli can mimic microenvironment dynamics where MSC‐Exo reside. These factors influence not only secretion but also, significantly, efficacy. Moreover, also serve as techniques engineering exosomes. Therefore, realm of assumes crucial role in modifying MSC‐Exo, ultimately facilitating translation. This review focuses on research progress applying to encompassing ultrasound, electrical stimulation, light irradiation, intrinsic properties, ionizing radiation, magnetic field, mechanical forces temperature. We discuss current status stimuli‐affected applications. Furthermore, we address limitations recent studies this field. Based this, provides insights advance refinement approach regenerative medicine.

Язык: Английский

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Proteomics of the heart

Physiological Reviews, Год журнала: 2024, Номер 104(3), С. 931 - 982

Опубликована: Фев. 1, 2024

Mass spectrometry-based proteomics is a sophisticated identification tool specializing in portraying protein dynamics at molecular level. Proteomics provides biologists with snapshot of context-dependent and proteoform expression, structural conformations, dynamic turnover, protein-protein interactions. Cardiac can offer broader deeper understanding the mechanisms that underscore cardiovascular disease, it foundational to development future therapeutic interventions. This review encapsulates evolution, current technologies, perspectives proteomic-based mass spectrometry as applies study heart. Key technological advancements have allowed researchers proteomes single-cell level employ robot-assisted automation systems for enhanced sample preparation techniques, increase fidelity spectrometers has unambiguous numerous posttranslational modifications. Animal models ranging from early animal experiments heart failure preserved ejection fraction, provided tools challenging organ laboratory. Further will pave way implementation even closer within clinical setting, allowing not only scientists but also patients benefit an interplay relates cardiac disease physiology.

Язык: Английский

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Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 30, 2025

Abstract Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these we overexpress the ICAM-1 binding receptor “lymphocyte function-associated antigen-1” (LFA-1) HEK293F sequential transfection of plasmids two LFA-1 subunits, ITGAL and ITGB2 (CD11a CD18). The was strongly overexpressed on EVs released transfected cells. We further loaded with therapeutic peptide, myeloid differentiation primary response 88 (Myd88; Myd88 ), through developed open-and-close procedure. is downstream common intracellular messenger for TLR-receptors. expression increases ICAM-1-expressing effect dose-dependently inhibited neutralizing antibody. Further, activated human endothelial treated had increased uptake EVs, resulting dose-dependent inhibition induced release IL-8, presumably Myd88. conclude LFA-1-expressing may be candidate suitable delivering peptides inflammatory diseases associated TLR-activation. Graphical

Язык: Английский

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Stabilized Extracellular Vesicle Formulations for Inhalable Dry Powder Development

Small, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Abstract Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with a significant impact on low‐ and middle‐income countries, making it critical challenge for global health equity sustainable development goals. Extracellular vesicles (EVs) are emerging as promising treatment COPD, but conventional storage at −80 °C limits their accessibility. This study explores alternative methods to enhance EV stability accessibility, particularly in low‐resource settings. EVs from lung fibroblasts subjected freezing, freeze drying, spray drying inulin or mannitol. The biophysical properties evaluated by capacity support organoid formation. Inulin proves effective stabilizing EVs, maintaining functionality after freezing −20 12 weeks. Freeze preserves 20 43% relative humidity. In contrast, mannitol exhibit aggregation reduce bio‐functionality. Additionally, leucine produces dry powder suitable inhalation, demonstrates efficient deposition using Cyclops inhaler. These findings suggest stabilizer eliminating need ultra‐low temperature improving practicality EV‐based inhalable therapies.

Язык: Английский

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Forging New Therapeutic Targets: Efforts of Tumor Derived Exosomes to Prepare the Pre-Metastatic Niche for Cancer Cell Dissemination and Dormancy

Biomedicines, Год журнала: 2023, Номер 11(6), С. 1614 - 1614

Опубликована: Июнь 1, 2023

Tumor-derived exosomes play a multifaceted role in preparing the pre-metastatic niche, promoting cancer dissemination, and regulating cell dormancy. A brief review of three types cells implicated metastasis an overview other extracellular vesicles related to are described. central focus this is on how influence progression throughout metastatic disease. Exosomes crucial mediators intercellular communication by transferring their cargo recipient cells, modulating behavior, tumor pro-gression. First, functional dissemination peripheral blood facilitating establishment pro-angiogenic pro-inflammatory niche described during organotro-pism lymphatic-mediated metastasis. Second, tumor-derived can transfer molecular signals that induce cycle arrest, dormancy, survival pathways disseminated dormant state reviewed. Third, several studies highlight exosome involvement maintaining cellular dormancy bone marrow endosteum. Finally, clinical implications as biomarkers or diagnostic tools for also outlined. Understanding complex interplay between developing novel therapeutic strategies target prevent recurrence. To end, examples nanocarriers used drug delivery system inhibit discussed. Strategies discussed alter content better loading capacity direct targeting integrins. Further, pre-clinical models Phase I trials implementing attack highlighted.

Язык: Английский

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