Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan‐Vesicular Affinity Probes DOI Creative Commons
Alessandro Gori, Roberto Frigerio, Paola Gagni

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(29)

Published: May 31, 2024

Abstract Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability concentrate protein biomarkers in bodily fluids. However, challenges isolating EVs from biological specimens hinder widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature poses challenges, as proposed markers may not be universally present thought, raising concerns about biomarker screening reliability. This issue extends EV‐mimics, where conventional lack applicability. Addressing these study reports on Membrane Sensing Peptides (MSP) pan‐vesicular affinity ligands for both non‐canonical analogs, streamlining capture phenotyping through Single Molecule Array (SiMoA). MSP enable circulating EVs, eliminating need prior isolation. Demonstrating clinical translation, technology detects an EV‐associated epitope signature serum plasma, distinguishing myocardial infarction stable angina. Additionally, allow tetraspanin‐lacking Red Blood Cell‐derived overcoming limitations associated antibody‐based methods. Overall, work underlines value complementary tools antibodies, advancing EV diagnostics beyond, marking first‐ever peptide‐based application SiMoA technology.

Language: Английский

Extracellular vesicles and nanoparticles: emerging complexities DOI Creative Commons
Dennis K. Jeppesen, Qin Zhang, Jeffrey L. Franklin

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(8), P. 667 - 681

Published: Feb. 1, 2023

The study of extracellular vesicles (EVs) and nanoparticles (NPs) is rapidly expanding because recent discoveries have revealed a much greater complexity diversity than was appreciated only few years ago. New types EVs NPs recently been described. Proteins nucleic acids previously thought to be packaged in exosomes appear more enriched different two identified amembranous NPs, exomeres supermeres. Thus, our understanding the cell biology intercellular communication facilitated by release state flux. In this review, we describe highlight advances, present major outstanding questions.

Language: Английский

Citations

355

Comprehensive isolation of extracellular vesicles and nanoparticles DOI Open Access
Qin Zhang, Dennis K. Jeppesen,

James N. Higginbotham

et al.

Nature Protocols, Journal Year: 2023, Volume and Issue: 18(5), P. 1462 - 1487

Published: March 13, 2023

Language: Английский

Citations

134

Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading DOI Creative Commons
Julia Rädler, Dhanu Gupta, Antje M. Zickler

et al.

Molecular Therapy, Journal Year: 2023, Volume and Issue: 31(5), P. 1231 - 1250

Published: Feb. 20, 2023

Extracellular vesicles (EVs) are gaining increasing attention for diagnostic and therapeutic applications in various diseases. These natural nanoparticles benefit from favorable safety profiles unique biodistribution capabilities, rendering them attractive drug-delivery modalities over synthetic analogs. However, the widespread use of EVs is limited by technological shortcomings biological knowledge gaps that fail to unravel their heterogeneity. An in-depth understanding biogenesis crucial unlocking full potential. Here, we explore how about EV can be exploited bioengineering load protein or nucleic acid cargos into onto EVs. We summarize more than 75 articles discuss findings on formation composition exosomes microvesicles, revealing multiple pathways may stimulation and/or cargo dependent. Our analysis further identifies key regulators loading this integrated develop engineered biotherapeutics.

Language: Английский

Citations

120

In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo DOI
Abi G. Yates, Ryan Pink,

Uta Erdbrügger

et al.

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 1, 2022

Abstract It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis most, if not all, normal physiological systems. However, majority our knowledge about EV signalling has come studying them disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis biofluids, obtained clinic, an essential work to improve understanding their interfere for therapeutic gain, more fundamental mechanisms by which they contribute pathogenic processes required. Only discovering how populations different biofluids change—size, number, and physicochemical composition—in clinical samples, may we then begin unravel functional roles translational models vitro vivo, can feedback clinic. In II review series, pathology will be discussed, focus on vivo evidence potential used as both biomarkers points intervention.

Language: Английский

Citations

110

L1CAM‐associated extracellular vesicles: A systematic review of nomenclature, sources, separation, and characterization DOI Creative Commons

Dimitria E. Gomes,

Kenneth W. Witwer

Journal of Extracellular Biology, Journal Year: 2022, Volume and Issue: 1(3)

Published: March 1, 2022

Abstract When released into biological fluids like blood or saliva, brain extracellular vesicles (EVs) might provide a window otherwise inaccessible tissue, contributing useful biomarkers of neurodegenerative and other central nervous system (CNS) diseases. To enrich for EVs in the periphery, however, cell‐specific EV surface markers are needed. The protein that has been used most frequently to obtain putative neuronal origin is transmembrane L1 cell adhesion molecule (L1CAM/CD171). In this systematic review, we examine existing literature on L1CAM EVs, including investigations both disease cancer through lens minimal information studies (MISEV), specifically domains nomenclature usage, sources, separation characterization. Although numerous have reported L1CAM‐associated biomarker signatures correlate with disease, interpretation these results complicated since expression not restricted neurons also upregulated during progression. A recent study suggested epitopes present biofluids mostly entirely as cleaved, soluble protein. Our findings practices trends L1CAM‐mediated separation, enrichment, characterization yield insights may assist interpreting results, evaluating rigor, suggesting avenues further exploration.

Language: Английский

Citations

80

Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine DOI Creative Commons
Min Li, Fang Fang, Meng Sun

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(11), P. 4879 - 4903

Published: Jan. 1, 2022

In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis tissue repair, have emerged one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review latest progress EVs applications. Firstly, will briefly introduce biogenesis, function isolation technology EVs. Then, underlying therapeutic mechanisms native unmodified engineering strategies modified entities be discussed. Subsequently, main focus placed on repair regeneration applications organs brain, heart, bone cartilage, liver kidney, well skin. More importantly, current clinical trials medicine also highlighted. Finally, future challenges insightful perspectives currently developed EV-based biomedicine short, opened new horizons biologists, chemists, nanoscientists, pharmacists, clinicians, making possible powerful tools therapies

Language: Английский

Citations

74

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

39

The biology and function of extracellular vesicles in immune response and immunity DOI
Raghu Kalluri

Immunity, Journal Year: 2024, Volume and Issue: 57(8), P. 1752 - 1768

Published: Aug. 1, 2024

Language: Английский

Citations

25

Extracellular vesicles as personalized medicine DOI Creative Commons
Danielle J. Beetler, Damian N. Di Florio, Katelyn A. Bruno

et al.

Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 91, P. 101155 - 101155

Published: Nov. 28, 2022

Extracellular vesicles (EVs) are released from all cells in the body, forming an important intercellular communication network that contributes to health and disease. The contents of EVs cell source-specific, inducing distinct signaling responses recipient cells. specificity their accumulation fluid spaces accessible for liquid biopsies make them highly attractive as potential biomarkers therapies duality favorable (therapeutic) or unfavorable (pathological) messengers is context dependent remains be fully determined homeostasis various disease states. This review describes use biomarkers, drug delivery vehicles, regenerative therapeutics, highlighting examples involving viral infections, cancer, neurological diseases. There growing interest provide personalized therapy based on individual patient characteristics. Increasing evidence suggests EV therapeutic approaches ideal medicine due diversity multifunctionality EVs.

Language: Английский

Citations

56

Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies DOI Creative Commons
Maimonah Eissa Al-Masawa, Mohammed Abdullah Alshawsh, Chiew Yong Ng

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(15), P. 6455 - 6508

Published: Jan. 1, 2022

Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We conducted systematic review available evidence assess sEV efficacy and safety in wound healing regeneration animal models. 68 studies were identified Web Science, Scopus, PubMed that satisfied set prespecified inclusion criteria. critically analyzed quality our criteria, with an emphasis on methodology, reporting, adherence relevant guidelines (including MISEV2018 ISCT criteria). Overall, meta-analysis indicated promoted diabetic non-diabetic models influenced various facets process regardless cell source, production protocol disease model. The EV isolation methods, dosing regimen, size varied among studies. Modification sEVs was achieved mainly by manipulating source cells via preconditioning, nanoparticle loading, genetic manipulation, biomaterial incorporation enhance potential. Evaluation potential adverse effects received only minimal attention, although none reported harmful events. Risk bias assessed SYRCLE's ROB tool uncertain most due insufficient limited. In summary, therapy has enormous However, reproducibility comprehensive evaluation are challenged general transparency reporting guidelines. Methodological rigor, standardization, risk analysis at all stages research needed promote translation clinical practice.

Language: Английский

Citations

51