Barcoded Hybrids of Extracellular Vesicles and Lipid Nanoparticles for Multiplexed Analysis of Tissue Distribution DOI Creative Commons
Alena Ivanova, Renata Chalupska, Ana F. Louro

et al.

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

Published: Jan. 16, 2025

Abstract Targeted delivery of therapeutic agents is a persistent challenge in modern medicine. Recent efforts this area have highlighted the utility extracellular vesicles (EVs) as drug carriers, given that they naturally occur bloodstream and tissues, can be loaded with wide range molecules. However, biodistribution tissue tropism EVs remain difficult to study systematically. Here, multiplexed approach developed for simultaneous tracking from various cell lines within single vivo experiment. are used 16 different lines, through controlled fusion lipid nanoparticles (LNPs) carrying single‐stranded DNA barcodes, uniquely barcoded hybrid EV particle (hEV) library generated. These hEVs combined profiling mice, discovered HAP1‐derived demonstrated lung tropism, suggesting these may targeted into tissue. To examine possibility further, it shown HAP1 hEV Cre mRNA displayed functional lungs. Overall, technology enables rapid across sources, which poised improve throughput extent studies, while reducing number animals required research.

Language: Английский

A beginner's guide to study extracellular vesicles in human blood plasma and serum DOI Creative Commons
Rienk Nieuwland, Pia Siljander

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 1, 2024

Abstract Blood is the most commonly used body fluid for obtaining and studying extracellular vesicles (EVs). While blood a standard choice clinical analysis, using as source of EVs introduces multiple layers complexity. At Extracellular Vesicle Workshop organized by International Society Vesicles in Helsinki (2022), it became evident that beginner researchers lack trustworthy information on how to initiate their research avoid common pitfalls. This educational guide explains composition frequently terminology blood, provides guidelines collection, preparation plasma serum. It also basic principles isolating detecting while considering blood‐related factors. The goal this assist beginners offering concise evidence‐based introduction current knowledge available resources study EVs.

Language: Английский

Citations

47

Extracellular Vesicles as Next-Generation Diagnostics and Advanced Therapy Medicinal Products DOI Open Access
Agnieszka Stawarska, Magdalena Bamburowicz‐Klimkowska, Elise Rundén‐Pran

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6533 - 6533

Published: June 13, 2024

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream downstream manufacturing processes EV large-scale production, also focusing on post-processing technologies such surface bioengineering uploading studies to yield novel EV-based diagnostics advanced therapy medicinal products. focuses the quality, safety, efficacy issues of bioengineered drug candidates before first-in-human studies. Because trials involving extracellular are global rise, this encompasses different registered clinical-trial register platforms, with varying levels advancement, highlighting growing interest in EV-related programs. Navigating regulatory affairs EVs poses real challenges, obtaining marketing authorization medicines remains complex due lack specific guidelines discusses state-of-the-art knowledge date products, further research needs safe reliable implementation tools settings. Post-marketing pharmacovigilance products is presented, mainly addressing topics risk assessment management.

Language: Английский

Citations

19

Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases DOI Creative Commons
Chenglong Wang,

Maochang Xu,

Qingze Fan

et al.

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

Citations

54

Regenerative potential of different extracellular vesicle subpopulations derived from clonal mesenchymal stem cells in a mouse model of chemotherapy-induced premature ovarian failure DOI
Nasim Eslami, Khadijeh Bahrehbar, Fereshteh Esfandiari

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 321, P. 121536 - 121536

Published: March 1, 2023

Language: Английский

Citations

27

Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine DOI Creative Commons
Dan Wu,

Xiansheng Zhao,

Jiaheng Xie

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(8)

Published: March 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.

Language: Английский

Citations

16

Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges DOI Open Access
Attila A. Seyhan

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7974 - 7974

Published: July 21, 2024

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans postoperative confirmation via histopathological molecular analysis. Imaging techniques struggle to differentiate between tumor progression treatment-related changes, leading potential misinterpretation delays. Similarly, tissue biopsies, while informative, are invasive not suitable for monitoring ongoing treatments. These challenges have led emergence liquid biopsy, through blood samples, a promising alternative monitoring. Presently, cerebrospinal fluid (CSF) sampling offers minimally means obtaining tumor-related information guide therapy. idea that any biofluid tests can be used screen many cancer types has huge potential. Tumors release various components into bloodstream other biofluids, including cell-free nucleic acids microRNAs (miRNAs), circulating DNA (ctDNA), cells (CTCs), proteins, extracellular vesicles (EVs) exosomes, metabolites, factors. factors been shown cross blood-brain barrier (BBB), presenting an opportunity well real-time assessment distinct genetic, epigenetic, transcriptomic, proteomic, metabolomic changes associated with brain tumors. their potential, clinical utility biopsy-based biomarkers is somewhat constrained by limitations absence standardized methodologies CSF collection, analyte extraction, analysis methods, small cohort sizes. Additionally, biopsies offer more precise insights morphology microenvironment. Therefore, objective biopsy should complement enhance diagnostic accuracy patients providing additional alongside traditional biopsies. Moreover, utilizing combination diverse biomarker may effectiveness compared solely relying one category, potentially improving sensitivity specificity addressing some existing GBM. This review presents overview latest research found in discusses diagnostic, predictive, prognostic indicators, future perspectives.

Language: Английский

Citations

15

Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma DOI Creative Commons
Bárbara Adem, Nuno Bastos, Carolina F. Ruivo

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 21, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood living systems. Here we use the genetically engineered mouse model (ExoBow) to map spatiotemporal distribution exosomes from healthy and PDAC pancreas vivo determine their biological significance. We show that, within microenvironment, cancer cells establish preferential communication routes through with associated fibroblasts endothelial cells. The latter being conserved event pancreas. Inhibiting secretion both scenarios enhances angiogenesis, underscoring contribution vascularization cancer. Inter-organ is significantly increased specific organs as most frequent targets occurring health thymus, bone-marrow, brain, intestines, kidneys, lungs thymus. In sum, find that mediate an organized intra- inter- network modulatory effects vivo.

Language: Английский

Citations

12

Exploring the Potential of Plant-Derived Exosome-like Nanovesicle as Functional Food Components for Human Health: A Review DOI Creative Commons
Yizhi Liu,

Chaoqin Ren,

Ruiling Zhan

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(5), P. 712 - 712

Published: Feb. 26, 2024

Plant-derived exosome-like nanovesicles (PELNs) are bilayer membrane-enclosed secreted by plant cells, serving as carriers of various substances such proteins, RNA, and metabolites. The mounting evidence suggests that PELN plays a crucial role in transmembrane signaling, nutrient transportation, apoptosis, regulation gut microbiota composition. This makes it promising "dark nutrient" for plants to modulate human physiology pathogenesis. A comprehensive understanding formation, uptake, functional mechanisms can offer novel insights into nutrition properties, thereby facilitating the precise development plant-based foods drugs. article provides summary extraction characterization, well absorption delivery processes. Furthermore, focuses on latest discoveries underlying physiological PELN's functions while exploring future research directions.

Language: Английский

Citations

12

Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety DOI Creative Commons
Yusuke Shimizu, Edward Hosea Ntege, Yoshikazu Inoue

et al.

Regenerative Therapy, Journal Year: 2024, Volume and Issue: 26, P. 260 - 274

Published: June 1, 2024

Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies CRISPR gene editing, microfluidic manufacturing, biomimetic systems are highlighted their potential enhance MSC-EV targeting, optimize enrichment, ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment tumorigenicity, immunogenicity, biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science patient advocacy hold the expediting clinical translation. By overcoming these challenges, could catalyze new era of off-the-shelf therapies, restoring hope afflicted by non-healing

Language: Английский

Citations

11

Quality and Safety Considerations for Therapeutic Products Based on Extracellular Vesicles DOI Creative Commons
Yoshinobu Takakura, Rikinari Hanayama, Kazunari Akiyoshi

et al.

Pharmaceutical Research, Journal Year: 2024, Volume and Issue: 41(8), P. 1573 - 1594

Published: Aug. 1, 2024

Extracellular vesicles (EVs) serve as an intrinsic system for delivering functional molecules within our body, playing significant roles in diverse physiological phenomena and diseases. Both native engineered EVs are currently the subject of extensive research promising therapeutics drug delivery systems, primarily due to their remarkable attributes, such targeting capabilities, biocompatibility, low immunogenicity mutagenicity. Nevertheless, clinical application is still a long way off owing multiple limitations. In this context, Science Board Pharmaceuticals Medical Devices Agency (PMDA) Japan has conducted comprehensive assessment identify current issues related quality safety EV-based therapeutic products. Furthermore, we have presented several examples state-of-the-art methodologies employed EV manufacturing, along with guidelines critical processes, production, purification, characterization, evaluation control, assessment, development therapeutics. These endeavors aim facilitate pave transformative impact healthcare.

Language: Английский

Citations

10