Extracellular vesicles in organ and systems function in health and disease DOI Open Access
Susan Currie, Harold D. Schultz

The Journal of Physiology, Год журнала: 2023, Номер 601(22), С. 4825 - 4829

Опубликована: Окт. 27, 2023

This special issue of The Journal Physiology entitled ‘Extracellular vesicles in organ and systems function health disease’ originated from a focused symposium held at Experimental Biology April 2021 sponsored by Physiological Society the American Society. original on extracellular (EVs) as targets for cardiovascular (CV) health, examining role EVs couriers cellular information well their therapeutic potential. Contributors provided range perspectives benefits limitations using biomedical applications. has widened scope to move beyond CV focus cover translational potential across multiple body systems. Articles include two Symposium Reviews, eight Topical six research papers along with Club article Perspective article. combination these contributions leading experts field EV provides valuable insight into our current understanding EVs, importantly, appraises future clinical application. opening review this succinct evaluation knowledge that play physiological pathophysiological processes systems, organs cell types (Alqurashi et al., 2023). There is useful summary classification according biological origin, most commonly known being exosomes (derived endosomal pathway), ectosomes via budding plasma membrane) apoptotic cells). Current recommendations also suggest classifying size if origin unclear. What clear overview sheer diversity subtypes existence, likelihood more subpopulations emerging future. growing carriers material, drugs, evident, critically challenges underlying application Importantly, authors highlight need improved fate vivo, protocols production monitoring Given technical surrounding use applications highlighted Alqurashi al. (2023), it timely one Reviews focuses adapting bioengineering approaches enhance features specifically (Malekian highlights some properties that, upon modification, could enable drug delivery. These modification donor cells transfection express specific surface proteins, exosome–liposome hybridisation alter lipid profile exosomes, ligand improve targeted detailed numerous recent used exosome raises possibility techniques advanced targeting. As such, resource investigators field. Four articles system. Two reviews are symposium. not only disease, but biomarkers pathologies tools provide complexity EV-mediated communication system impact cargo can have function. consideration strengths strategies therapeutics outlined reader an awareness key focus. between different essential maintain healthy lead pathological consequences. Martins-Marques Girao (2023) how released populations influence neighbouring cardiomyocytes, cardiac fibroblasts, endothelial macrophages among considered, fascinating reflect cardioprotection. consider evidence mediating remodelling including myocardial infarction, hypertrophy fibrosis, atrial fibrillation. Aligned pathology, predictors risk. builds previous Osteikoetxea (2016) who importance source quantity system, suggesting numbers may ultimately be cardioprotective or pathogenic. In complementary Review, Neves emphasise correlation circulating risk severity disease. micro (mi)RNAs cardioprotection pathology disease biomarkers. attractive (low immunogenicity toxicity strong ability cross membranes) lend themselves raise delivery since loading desired (drugs, miRs, proteins) interfere structure therefore target host. They area development order design effective exosome-based methods Delving further mediate function, there Review included non-coding (nc)RNAs (Collado ncRNAs long (lnc)RNAs, miRNAs circular (circ)RNAs. contains very diagrams outlining many varied effects EV-derived both atherosclerosis progression coronary artery ischaemic heart fibrosis. accompanying text wide references covering complex cell–cell communication. previously reiterates characterise size, morphology concentration. present advantages disadvantages classical isolation, differential centrifugation, density gradient ultracentrifugation, size-exclusion chromatography, precipitation immunocapture. new approaches, atomic force microscopy, Raman spectroscopy, latter enabling characterisation content all one. theme characterise, image monitor comprises second (Ranjan associated designing therapeutics, short half-life adverse off-target effects. Efficient targeting challenge context Connexin 43, widely expressed gap junction protein (prevalent cardiomyocytes), exosomal contents and, when protein, protection against cardiotoxic drugs. reinforces connexin 43 (2023). Ranjan report studies cardiosphere-derived stem cell-derived shown repair, they stress delivering number required purposes demanding still uncertainty around actual content/cargo. track vivo another researchers covers currently used, such covalent binding tagged molecules surface, genetic modulation, metabolic labelling real-time imaging radiolabelling. methodology does tracking sub-populations carrying secreted same EV-based rely advances where lie. treatment acute stroke covered (Fullerton derived mesenchymal restoring neurological following stroke. similar vein relating details individual (including miRNA-124, miRNA-126, miRNA-98, miRNA-146 miRNA-181a) recovery. It significant alterations occur miRNA people experienced stroke, discuss those diagnostic prognostic emphasised methodological analytical isolation characterisation, example differences timing sampling, storage procedures accounting physiology. That said, even taking account, do appear common signatures changes indicates neuroregenerative therapy over cells. Since delivered systemically (they blood–brain barrier), favourable preclinical models look promising. liver (Srinivas show promise conditions viral hepatitis, fatty cancer. mainly stems large prospective trials pilot studies. hepatic laboratory modulation reduce certain pathologies. For example, GW4869, which pharmacological inhibitor release, increase transmission uninfected SHP099 (a SHP2 inhibitor) release pro-fibrogenic thus potentially reducing though lie fact inhibitors selective diseased vehicles treating seen nucleic acid-loaded siRNA gene silencing artificial exosome-mimetic nanovesicles, overcome low yields often isolated under conditions. paper, Chen investigate macrophage microvesicles (MMVs) intercellular lung MMVs carry transfer variety acids, proteins lipids study examines circRNAs chronic injury, injury induced methamphetamine (MA) abuse. paper first examine lncRNAs circ_YTHDF2 MMV-mediated alveolar uses primary material mouse model MA, bronchoalveolar lavage fluid MMVs) Results predominant form extracted culture. Following long-term MA (6 weeks mice up 24 h culture), increased apparent interestingly, uptake A heatmap circRNA microarray identifies significantly altered treatment. Knockdown control results levels tumour necrosis factor α, interleukin 6 adhesion molecule 1, indicating regulates immunoreactivity MMVs. By exploring cells, demonstrate si-circ_YTHDF2 exacerbate MA-induced inflammatory transition aortic Overexpression reverses injury. effectively demonstrates within supports Collado emphasising processes. terms other involved process. exponentially. One remains limited, yet hold tremendous potential, pregnancy. Farrelly literature investigating placental maternal pregnancy complications, pre-eclampsia, preterm birth, fetal growth restriction complications arising gestational diabetes. serves important gaps exist. During pregnancy, placenta enables bidirectional trafficking, enter vice versa. predict and/or diagnose Reported diabetes pre-eclampsia predictive diagnosis. possible alleviate dysfunction observed pre-eclampsia. normal induction labour term mechanisms birth. cause perinatal morbidity mortality, urgent intervention. administration pro-inflammatory pregnant day 15 resulted premature Studies humans found number, distribution during trimesters vary pregnancies go preterm. real lack treatment, basic clinicians obstetrics. roles exercise age physiology health. ageing five papers. explore pathophysiology, aged young individuals, separation identification individuals undergoing training. reports recovering muscle after disuse. Taken together, physiologists older McIlvenna Whitman small (sEVs), microparticles, process, this. Cellular senescence, occurring part ageing, involves factors senescence-associated secretory phenotype (SASP). contribution sEVs make SASP process clear, particularly suggests sEV reflected host senescent contributing human pluripotent (iPSCs) reverse anti-oxidant capacity iPSCs property, properly define ensure standardised. recurring message throughout 2023; Fullerton Srinivas promote remain elusive. cargos TMSB4X (important generation), glutathione peroxidase superoxide dismutase (both antioxidants) upregulated exercise. value proteomic datasets gather data deposited, will grow, guiding area. Five implications Together, give what vast intriguing high intensity intermittent training (HIIT) platelet-poor platelet-free plasma. Echoing views issue, standardised technique interpretation. particular, contaminating remnant platelets have. incorporated assessment single particle analysis, circumvents sample purification, platelet poor free HIIT alters expression tetraspanin proteins. Interestingly, depletion influences tetraspanins before analysis isolation. Another resting differ histories affect interpretation data. Darragh three groups (all male) were recreationally active, endurance trained strength trained. various identification, nanoparticle flow cytometry immunoblotting markers metabolomics performed each participant. blood samples comparable. work should males females thorough nonetheless, physiologists, inform confirming rest. Several type 2 ageing. reviewed recently Vechetti (2021) highlighting skeletal must communicate distal tissues through endocrine functions. prospect communicators route. Heiston aerobic decrease concentration fasting insulin-stimulated medium obese individuals. Previous suggested obesity indicate parallel lowered decreases AIx75 marker arterial stiffness) increases insulin sensitivity. EV–insulin interaction. paves way exercise-induced states. Indeed, (such miR-15a, miR22, miR-92a, miR122 miR-192) been positively correlate (Brandao 2023) would impacted addition beneficial conditions, mounting positive Xhuti examined resistance (12 weeks) (exosome-like (ELVs) ectosomes) ELV cargo. shows Circulating CD81+ CD9+ ELVs reduced (myomiRs) lower (miR-23a miR-27a). true circulation biopsies taken vitro myotube model. normalise back consistent young, subjects. article, Hamrick stresses findings reported notes rigor enabled detail subpopulation miR-23a 27a downregulation reversed result since, notes, Dicer (which plays biogenesis) group so global effect. effect miRs serve frailty intervention Wang analysed commended. echoes points made emphasises exclusion subsequent ultracentrifugation α-sarcoglycan identify muscle. have, elderly unable regularly effectively. Both note approach aid recovery disuse, explored Wu resident perivascular stromal (pericytes) produce antioxidant anti-inflammatory factors, acting natural defence damage. Using unilateral hindlimb immobilisation, RNA sequencing combined functional confirm response pericytes immobilised impaired. strategy priming H2O2, injection primed collagen myofibre immobilisation. unprimed pericytes. While proteome, determine exact responsible lies considerably research. reference sub-disciplines shed light perspective avenues lie, available EVs. Going forward, collection constructive basis direction Lastly, we pleased acknowledge published prior vesicles, microparticles 2015 Cardiff, UK 2015. (Krohn 2016; Morrison Ruiz 2016) additional related topics. Please note: publisher functionality any supporting supplied authors. Any queries (other than missing content) directed corresponding author No competing interests declared. S.C. H.S.: conception drafting revising intellectual content. read approved final version manuscript agree accountable aspects ensuring questions accuracy integrity appropriately investigated resolved. All persons designated qualify authorship, authorship listed. funding was received work.

Язык: Английский

Molecular insights of exercise therapy in disease prevention and treatment DOI Creative Commons
David Walzik, Tiffany Y. Wences Chirino, Philipp Zimmer

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 29, 2024

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for prevention and treatment various diseases, underlying biological mechanisms have not been fully elucidated. Several attributed to signaling molecules that are released in response by different tissues such as skeletal muscle, cardiac adipose, liver tissue. These molecules, which collectively termed exerkines, form a heterogenous group bioactive substances, mediating inter-organ crosstalk well structural functional tissue adaption. Numerous scientific endeavors focused on identifying characterizing new mediators with properties. Additionally, some investigations molecular targets exerkines cellular cascades trigger adaption processes. A detailed understanding tissue-specific downstream effects is crucial harness health-related mediated improve targeted programs health disease. Herein, we review current vivo exerkine-induced signal transduction across multiple target highlight preventive therapeutic value exerkine diseases. By aspects research, provide comprehensive overview (i) underpinnings secretion, (ii) receptor-dependent receptor-independent adaption, (iii) clinical implications these disease treatment.

Язык: Английский

Процитировано

12

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise DOI Creative Commons
Ludovic Giloteaux, Katherine A. Glass, Arnaud Germain

и другие.

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(1)

Опубликована: Янв. 1, 2024

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue reduces the risk of chronic diseases. Although is suggested as a lifestyle intervention to manage various illnesses, it negatively affects people with myalgic encephalomyelitis/chronic syndrome (ME/CFS), who suffer from intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an challenge may contribute their prolonged exacerbated negative response exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography plasma 18 female 17 age- BMI-matched sedentary controls at three time points: before, 15 min, 24 h maximal cardiopulmonary test. characterized using nanoparticle tracking analysis protein cargo was quantified Tandem Mass Tag-based (TMT) proteomics. The results show EV proteome differently than individuals changes proteins are strongly correlated symptom severity ME/CFS. Differentially abundant versus involved many pathways systems, including coagulation processes, contraction (both smooth skeletal muscle), cytoskeletal proteins, immune system brain signalling.

Язык: Английский

Процитировано

7

Extracellular vesicle transfer of miR-1 to adipose tissue modifies lipolytic pathways following resistance exercise DOI Creative Commons
Benjamin I. Burke, Ahmed Ismaeel, Douglas E. Long

и другие.

JCI Insight, Год журнала: 2024, Номер 9(21)

Опубликована: Сен. 24, 2024

Extracellular vesicles (EVs) have emerged as important mediators of intertissue signaling and exercise adaptations. In this human study, we provide evidence that muscle-specific microRNA-1 (miR-1) was transferred to adipose tissue via EVs following an acute bout resistance exercise. Using a multimodel machine learning automation tool, discovered muscle primary miR-1 transcript CD63+ EV count in circulation top explanatory features for changes levels response RNA-Seq in-silico prediction target genes identified caveolin 2 (CAV2) tripartite motif containing 6 (TRIM6) downregulated the subset participants with highest increases Overexpression differentiated adipocyte-derived stem cells these targets enhanced catecholamine-induced lipolysis. These data identify potential EV-mediated mechanism by which skeletal communicates modulates lipolysis miR-1.

Язык: Английский

Процитировано

5

From sweat to hope: The role of exercise‐induced extracellular vesicles in cancer prevention and treatment DOI Creative Commons
Alicia Llorente,

Agnese Brokāne,

Agata Mlynska

и другие.

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(8)

Опубликована: Авг. 1, 2024

Abstract The benefits of regular physical exercise on cancer prevention, as well reducing fatigue, treatment side effects and recurrence, improving quality life overall survival patients, are increasingly recognised. Initial studies showed that the concentration extracellular vesicles (EVs) increases during activity EVs carry biologically active cargo. These released by blood cells, skeletal muscle other organs involved in exercise, thus suggesting may mediate tissue crosstalk exercise. This possibility triggered a great interest study roles systemic adaptation to their potential applications prevention various diseases, including cancer. review presents exploring molecular cargo Furthermore, we discuss putative stimuli trigger EV release from cell types, biological functions impact exercise‐induced development progression. Understanding interplay between EVs, biology offer insights into novel therapeutic strategies preventive measures for

Язык: Английский

Процитировано

4

Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice DOI Creative Commons
Oliver K Fuller, Emma McLennan,

Casey L. Egan

и другие.

iScience, Год журнала: 2025, Номер 28(2), С. 111752 - 111752

Опубликована: Янв. 5, 2025

Exercise improves cognitive function in Alzheimer's disease (AD) via mechanism that are not fully clear. Here, we first examined the effect of voluntary exercise training (VET) on energy metabolism and APP/PS1 transgenic mouse (Tg) model familial AD. Next, profiled extracellular vesicles (EVs) whether they may play a role protective effects VET intranasal administration EVs, purified from blood sedentary (sEV) and/or acutely exercised (eEV) donor wild-type mice into APP/PS1Tg mice. We show reduced resting expenditure (REE) improved cognition Tg Administration eEV, but sEV, also REE, had no cognition. Taken together, these data is effective intervention to improve symptoms AD In addition, eEVs mediate some effects, implicating EVs treatment age-related neurodegenerative diseases.

Язык: Английский

Процитировано

0

Mapping organism-wide single cell mRNA expression linked to extracellular vesicle biogenesis, secretion and cargo DOI Creative Commons
Thomas J. LaRocca, Daniel S. Lark

Function, Год журнала: 2025, Номер unknown

Опубликована: Янв. 25, 2025

Abstract Extracellular vesicles (EVs) are functional lipid-bound nanoparticles trafficked between cells and found in every biofluid. It is widely claimed that EVs can be secreted by cell, but the quantity composition of these differ greatly among cell types tissues. Defining this heterogeneity has broad implications for EV-based communication health disease. Recent discoveries have linked single-cell EV secretion to expression genes encoding machinery cargo. To gain insight at resolution across an entire organism, we compared abundance, variance co-expression 67 involved biogenesis secretion, or carried as cargo, >44,000 obtained from 117 populations Tabula Muris.

Язык: Английский

Процитировано

0

Extracellular vesicles: their challenges and benefits as potential biomarkers for musculoskeletal disorders DOI Creative Commons
Soo‐Eun Sung, Min‐Soo Seo,

Wook Tae Park

и другие.

Journal of International Medical Research, Год журнала: 2025, Номер 53(2)

Опубликована: Фев. 1, 2025

Early diagnosis and timely management are critical for determining disease outcomes prognoses. To date, certain methods developing disease-specific biomarkers have been reported; however, strategies musculoskeletal biomarker development rarely studied. Recent studies highlighted the potential application of extracellular vesicles (EVs) as biomarkers. EVs encapsulate proteins, lipids, messenger RNAs, microRNAs derived from their cellular origin; these constituents remain stable within can traverse blood–brain barrier. Because distinctive characteristics, actively investigated diagnostic tools various conditions, including cancer, inflammatory diseases, disorders. Although many advantages development, they not yet fully researched in context pathologies. The current review aimed to highlight biomarkers, summarize processes EV discuss limitations future perspectives

Язык: Английский

Процитировано

0

Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants DOI Creative Commons
Peijie Wu, Wenjun Wu, Shu Zhang

и другие.

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Дек. 1, 2023

Medicinal plants are the primary sources for discovery of novel medicines and basis ethnopharmacological research. While existing studies mainly focus on chemical compounds, there is little research about functions other contents in medicinal plants. Extracellular vesicles (EVs) functionally active, nanoscale, membrane-bound secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular (PDEVs) also have been implicated to play an important role therapeutic application. PDEVs were reported physical properties similar mammalian EVs, which rich lipids, proteins, nucleic acids, pharmacologically active compounds. Besides these properties, exhibit unique advantages, especially intrinsic bioactivity, high stability, easy absorption. found be transferred into recipient cells significantly affect their biological process involved many diseases, such as inflammation tumors. could offer morphological compositional characteristics natural nanocarriers innately shuttling bioactive RNA, substances. In addition, effectively encapsulate hydrophobic hydrophilic chemicals, remain stable, cross stringent barriers. Thus, this study focuses pharmacological action mechanisms applications. We systemically deal with facets PDEVs, ranging from isolation composition, functions, biotherapeutic roles. Efforts made elucidate recent advances re-engineering applied effective, non-immunogenic applications meet ever-stringent demands. Considering its not only provide relevant scientific evidence but replenish inherit precious cultural heritage.

Язык: Английский

Процитировано

10

Predicting cell type-specific extracellular vesicle biology using an organism-wide single cell transcriptomic atlas – insights from theTabula Muris DOI Creative Commons
Thomas J. LaRocca, Daniel S. Lark

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 21, 2024

ABSTRACT Extracellular vesicles (EVs) like exosomes are functional nanoparticles trafficked between cells and found in every biofluid. An incomplete understanding of which cells, from tissues, trafficking EVs vivo has limited our ability to use as biomarkers therapeutics. However, recent discoveries have linked EV secretion expression genes proteins responsible for biogenesis cargo, suggests that emerging “cell atlas” datasets could be used begin biology at the level organism possibly rare cell populations. To explore this possibility, here we analyzed 67 directly implicated secretion, or carried ∼44,000 obtained 117 populations Tabula Muris . We most abundant cargo (tetraspanins syndecans) were also expressed across all populations, but these varied greatly among Expression variance analysis identified dynamic constitutively with implications secretion. Finally, gene co-expression define population-specific transcriptional networks. Our is first, knowledge, predict tissue- type-specific As such, expect resource first many valuable tools predicting endogenous impact specific on function health disease.

Язык: Английский

Процитировано

1

Study protocol for the ROLEX-DUO randomised placebo-controlled trial: ROmosozumab Loaded with EXercise – DUal effects on bone and muscle in postmenopausal Osteoporosis and Osteopenia DOI Creative Commons
Shejil Kumar, Belinda R. Beck,

Liza Nery

и другие.

BMJ Open, Год журнала: 2024, Номер 14(8), С. e086708 - e086708

Опубликована: Авг. 1, 2024

Introduction Novel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance impact (HiRIT) exercise has shown benefit in improving bone density postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance therapeutic effects pharmacotherapy not been established. ROLEX-DUO is a randomised controlled trial designed assess efficacy romosozumab on various muscle outcomes combination different interventions Methods analysis an 8-month placebo-controlled conducted at two tertiary referral centres for patients osteoporosis/osteopenia Sydney, New South Wales, Australia. The study implementing or placebo forms without recent fracture (n=102). Eligible will be 1:1:1 into one three groups: (1) supervised HiRIT, (2) unsupervised low-intensity (3) exercise. Co-primary mean percentage change lumbar spine mineral (BMD), five times sit-to-stand test performance (seconds) 8 months. Secondary/exploratory include BMD changes femoral neck, total hip distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) outcomes, DXA-derived lean fat mass, serum markers turnover (procollagen type 1 peptide, C-telopeptide collagen) biomarkers (dickkopf-1), extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom number falls Mixed-effects models performed compare longitudinal outcome results between groups using intention-to-treat analysis. Ethics dissemination was approved by Northern Sydney Local Health District Human Research Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants provide written informed consent prior inclusion. Findings disseminated via peer-reviewed journals, scientific conferences summary reports funding bodies. Trial registration ACTRN12623000867695.

Язык: Английский

Процитировано

1