Journal of extracellular biology最新文献

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Monitoring concentration and lipid signature of plasma extracellular vesicles from HR+ metastatic breast cancer patients under CDK4/6 inhibitors treatment CDK4/6抑制剂治疗下HR+转移性乳腺癌患者血浆细胞外囊泡浓度和脂质特征监测
Journal of extracellular biology Pub Date : 2024-12-17 DOI: 10.1002/jex2.70013
Mathilde Richard, Rosalie Moreau, Mikaël Croyal, Laurent Mathiot, Jean-Sébastien Frénel, Mario Campone, Aurélien Dupont, Julie Gavard, Gwennan André-Grégoire, Laëtitia Guével
{"title":"Monitoring concentration and lipid signature of plasma extracellular vesicles from HR+ metastatic breast cancer patients under CDK4/6 inhibitors treatment","authors":"Mathilde Richard,&nbsp;Rosalie Moreau,&nbsp;Mikaël Croyal,&nbsp;Laurent Mathiot,&nbsp;Jean-Sébastien Frénel,&nbsp;Mario Campone,&nbsp;Aurélien Dupont,&nbsp;Julie Gavard,&nbsp;Gwennan André-Grégoire,&nbsp;Laëtitia Guével","doi":"10.1002/jex2.70013","DOIUrl":"10.1002/jex2.70013","url":null,"abstract":"<p>Extracellular vesicles (EVs) are cell-derived small membrane structures that transport various molecules. They have emerged as potential circulating biomarkers for monitoring responses to cancer therapies. This study aimed to comprehensively characterize plasma-carried EVs in hormone receptor-positive (HR<sup>+</sup>) metastatic breast cancer (MBC) patients treated with first-line CDK4/6 inhibitors (iCDK4/6) combined with endocrine therapy. MBC patients were classified into three groups based on their response to therapy: resistant, intermediate or sensitive. In a prospective cohort, we monitored the concentration of circulating EVs, analyzed their lipid signature and correlated these factors with treatment response. To facilitate the translation of EV research to clinical practice, we established a three-step procedure: (1) EVs were isolated from plasma using semi-automatized size exclusion chromatography (SEC); (2) EV concentration, termed vesiclemia, was determined by drop counting via interferometric light microscopy (ILM); and (3) EV lipid composition was analyzed by mass spectrometry. ILM-based vesiclemia values were highly fluctuating upon iCDK4/6 treatment, while early increase associated with accelerated progression. Of note, vesiclemia remained a steady parameter over a 1-year period in age-matched healthy women. Additionally, analysis of the EV cargo unveiled a distinct sphingolipid profile, characterized by increased levels of ceramides and sphingomyelins in resistant patients within the first 2 months of treatment. Based on 16 sphingolipid species, sensitive and resistant patients were correctly classified with an overall accuracy of 82%. This specific sphingolipid pattern was exclusively discernible within EVs, and not in plasma, highlighting the significance of EVs in the early prediction of individual responses to iCDK4/6 and disease progression. Overall, this study provides insights of the longitudinal characterization of plasma-borne EVs in both a healthy group and HR<sup>+</sup> MBC patients under iCDK4/6 therapies. Combined vesiclemia and EV sphingolipid profile emphasize the promising potential of EVs as non-invasive biomarkers for monitoring early treatment response.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Spirulina-derived extracellular vesicles and their potential as a vaccine adjuvant 螺旋藻衍生的细胞外囊泡的特性及其作为疫苗佐剂的潜力。
Journal of extracellular biology Pub Date : 2024-12-12 DOI: 10.1002/jex2.70025
Mohammad Farouq Sharifpour, Suchandan Sikder, Yide Wong, Na'ama Koifman, Tamara Thomas, Robert Courtney, Jamie Seymour, Alex Loukas
{"title":"Characterization of Spirulina-derived extracellular vesicles and their potential as a vaccine adjuvant","authors":"Mohammad Farouq Sharifpour,&nbsp;Suchandan Sikder,&nbsp;Yide Wong,&nbsp;Na'ama Koifman,&nbsp;Tamara Thomas,&nbsp;Robert Courtney,&nbsp;Jamie Seymour,&nbsp;Alex Loukas","doi":"10.1002/jex2.70025","DOIUrl":"10.1002/jex2.70025","url":null,"abstract":"<p>Spirulina is an edible cyanobacterium that increasingly gaining recognition for it untapped potential in the biomanufacturing of pharmaceuticals. Despite the rapidly accumulating information on extracellular vesicles (EVs) from most other bacteria, nothing is known about Spirulina extracellular vesicles (SPEVs). This study reports the successful isolation, characterization and visualization of SPEVs for the first time and it further investigates the potential therapeutic benefits of SPEVs using a mouse model. SPEVs were isolated using ultracentrifugation and size-exclusion-chromatography. Cryo-Transmission Electron Microscopy revealed pleomorphic outer-membrane-vesicles and outer-inner-membrane-vesicles displaying diverse shapes, sizes and corona densities. To assess short- and long-term immune responses, mice were injected intraperitoneally with SPEVs, which demonstrated a significant increase in neutrophils and M1 macrophages at the injection site, indicating a pro-inflammatory effect induced by SPEVs without clinical signs of toxicity or hypersensitivity. Furthermore, SPEVs demonstrated potent adjuvanticity by enhancing antigen-specific IgG responses in mice by over 100-fold compared to an unadjuvanted model vaccine antigen. Mass-spectrometry identified 54 proteins within SPEVs, including three protein superfamily members linked to the observed pro-inflammatory effects. Our findings highlight the potential of SPEVs as a new class of vaccine adjuvant and warrant additional studies to further characterize the nature of the immune response.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of electric fields on the release and content of extracellular vesicles 电场对细胞外囊泡释放和含量的影响
Journal of extracellular biology Pub Date : 2024-11-29 DOI: 10.1002/jex2.70018
Yihua Wang, Gregory A. Worrell, Hai-Long Wang
{"title":"Effects of electric fields on the release and content of extracellular vesicles","authors":"Yihua Wang,&nbsp;Gregory A. Worrell,&nbsp;Hai-Long Wang","doi":"10.1002/jex2.70018","DOIUrl":"10.1002/jex2.70018","url":null,"abstract":"<p>Extracellular vesicles (EVs) are small membrane-bound structures that originate from various cell types and carry molecular cargos to influence the behaviour of recipient cells. The use of EVs as biomarkers for diagnosis and as delivery vehicles for treatment in a wide range of human disease is a rapidly growing field in research and clinical practice. We hypothesized that electric fields (EFs) could influence the release and content of EVs. To examine this hypothesis, we developed a specialized bioreactor enabling cells to thrive in a three-dimensional setting, replicating in-vivo conditions amidst programmable EF environments. We established a three-step EV purification protocol to achieve high-density production of EVs. We also performed mass spectrometry-based proteomics analysis on EV-carrying proteins and used high-resolution nanoparticle flowcytometry for single-vesicle analysis. Findings from this report suggest that electrical stimulation, employing physiologically relevant amplitudes typical in therapeutic deep brain stimulation, influences the release of EVs and their cargo content in a frequency-dependent fashion. This conclusion could carry significant implications for both fundamental biological understanding and medical advancements. First, it raises an intriguing question about how the endogenous electrical activity of neuronal and other cellular assemblies influence the production and composition of EVs. Second, it reveals a novel underlying mechanism of how therapeutic electrical stimulations can modulate EVs and treat human brain disorders. Third, it provides a novel approach to utilize electrical stimulation for generating desired EV cargos in a programmable setting.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes 胰岛细胞中多泡体和分泌颗粒的定位和释放的比较:2型糖尿病的失调
Journal of extracellular biology Pub Date : 2024-11-29 DOI: 10.1002/jex2.70014
Priyadarshini Veerabhadraswamy, Kiran Lata, Sristi Dey, Prajakta Belekar, Lakshmi Kothegala, Vidya Mangala Prasad, Nikhil R. Gandasi
{"title":"Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes","authors":"Priyadarshini Veerabhadraswamy,&nbsp;Kiran Lata,&nbsp;Sristi Dey,&nbsp;Prajakta Belekar,&nbsp;Lakshmi Kothegala,&nbsp;Vidya Mangala Prasad,&nbsp;Nikhil R. Gandasi","doi":"10.1002/jex2.70014","DOIUrl":"10.1002/jex2.70014","url":null,"abstract":"<p>Multivesicular bodies (MVBs) are vesicles of endosomal origin containing intraluminal vesicles, which upon fusion with plasma membrane, secrete exosomes. They play a significant role in the physiology and pathology of type-2 diabetes (T2D) due to disrupted intercellular communication. The role of MVBs and their influence on insulin secretory granules (ISGs) of β-cells or their characterization is yet to be uncovered. In our study, we compared MVBs to largely well-characterized ISGs in β-cells. This study compares the density, localization, and exocytosis of CD63+ compartments (CD63+c) with NPY labelled ISGs (NISGs) in β-cells. For this, tetraspanin CD63 was exploited to majorly label MVBs in β-cells. These labels preserve the structural integrity of labelled compartments and mostly do not localize with other endo-lysosomal compartments. This study showed that the β-cells have a significantly higher density of NISGs than CD63+c. CD63+c and NISGs are spatially localized apart within β-cells. The proteins that localize with CD63+c are different from the ones that localize with NISGs. Exocytosis of NISGs occurs at the periphery of the β-cells and takes significantly less time when compared to the release of CD63+c, which is non-peripheral and takes a longer duration. Mechanistically, the availability of CD63+c for exocytosis was assessed and found that an equilibrium is maintained between docking and undocking states at the plasma membrane. Although there are a high number of short-term residing, visiting CD63+c at the plasma membrane, the availability of CD63+c for exocytosis is maintained due to docking and undocking states. Further, a significant reduction in the density of NISGs and CD63+c was observed in β-cells isolated from T2D donors compared to healthy counterparts. Studying the effect of MVBs on insulin secretion in physiological and T2D conditions has huge potential. This study provides a strong basis to open new avenues for such future studies.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uromodulin and the study of urinary extracellular vesicles 尿囊素与尿液细胞外囊泡研究
Journal of extracellular biology Pub Date : 2024-11-22 DOI: 10.1002/jex2.70022
Michael A. Harding, Hayrettin Yavuz, Annika Gathmann, Samantha Upson, Agnieszka Swiatecka-Urban, Uta Erdbrügger
{"title":"Uromodulin and the study of urinary extracellular vesicles","authors":"Michael A. Harding,&nbsp;Hayrettin Yavuz,&nbsp;Annika Gathmann,&nbsp;Samantha Upson,&nbsp;Agnieszka Swiatecka-Urban,&nbsp;Uta Erdbrügger","doi":"10.1002/jex2.70022","DOIUrl":"10.1002/jex2.70022","url":null,"abstract":"<p>Urinary extracellular vesicles (uEVs) are a promising substrate for discovering new biomarkers. In order to investigate the origin of uEVs and the cargo they carry, some types of downstream analysis of uEVs may require concentration and enrichment as well as removal of contaminating substances. Co-isolation of the abundant urinary protein uromodulin with uEVs can be a problem, and may interfere with some techniques, in particular with proteomic analysis tools. Methods of separating out uromodulin and its removal have also not been standardized. This review highlights aspects of uromodulin structure that makes it recalcitrant to separation from uEVs, summarizes frequently used techniques for uEV enrichment and how they affect uromodulin separation, and specific methods for uromodulin removal during preparation of uEVs. The necessity of uromodulin removal for various study endpoints is also examined.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Size matters: Biomolecular compositions of small and large extracellular vesicles in the urine of glioblastoma patients 大小很重要:胶质母细胞瘤患者尿液中大小细胞外囊泡的生物分子组成
Journal of extracellular biology Pub Date : 2024-11-15 DOI: 10.1002/jex2.70021
Susannah M. Hallal, Liam A. Sida, Ágota Tűzesi, Brindha Shivalingam, Hao-Wen Sim, Michael E. Buckland, Laveniya Satgunaseelan, Kimberley L. Alexander
{"title":"Size matters: Biomolecular compositions of small and large extracellular vesicles in the urine of glioblastoma patients","authors":"Susannah M. Hallal,&nbsp;Liam A. Sida,&nbsp;Ágota Tűzesi,&nbsp;Brindha Shivalingam,&nbsp;Hao-Wen Sim,&nbsp;Michael E. Buckland,&nbsp;Laveniya Satgunaseelan,&nbsp;Kimberley L. Alexander","doi":"10.1002/jex2.70021","DOIUrl":"10.1002/jex2.70021","url":null,"abstract":"<p>The promise of urinary extracellular vesicles (uEVs) in biomarker discovery is emerging. However, the characteristics and compositions of different uEV subpopulations across normal physiological and pathological states require rigorous explication. We recently reported proteomic signatures of small (s)-uEVs (&lt;200 nm membranous nanoparticles) and described putative biomarkers corresponding to the diagnosis, tumour burden and recurrence of the lethal adult primary brain tumour, glioblastoma. Here, we comprehensively characterise uEV populations with significantly different mean and mode particle sizes obtained by differential centrifugation at 100,000 × <i>g</i> (100K-uEVs; smaller) and 17,000 × <i>g</i> (17K-uEVs; larger) using Fourier-transform infrared spectroscopy and quantitative data-independent acquisition mass spectrometry. We show distinct differences in protein and lipid content, prominent protein secondary structures, and proteome distributions between uEV populations that can distinguish glioblastoma patients from healthy controls and correspond to clinically relevant tumour changes (i.e., recurrence and treatment resistance). Among the key findings is a putative seven-protein biomarker panel associated with 17K-uEVs that could distinguish all glioblastoma patients from healthy controls and accurately classify 98.2% of glioblastoma samples. These novel, significant findings demonstrate that both uEV populations offer individual and combined biomarker potential. Further research is warranted to elucidate the complete diagnostic, prognostic, and predictive capabilities of often-neglected 17K-uEV populations.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of bovine milk exosome preparation and lyophilized powder stability 牛乳外泌体制备和冻干粉稳定性评估
Journal of extracellular biology Pub Date : 2024-11-15 DOI: 10.1002/jex2.70009
Lu Lu, Chunle Han, Miao Wang, Huanqing Du, Ning Chen, Mengya Gao, Na Wang, Dongli Qi, Wei Bai, Jianxin Yin, Fengwei Dong, Tianshi Li, Xiaohu Ge
{"title":"Assessment of bovine milk exosome preparation and lyophilized powder stability","authors":"Lu Lu,&nbsp;Chunle Han,&nbsp;Miao Wang,&nbsp;Huanqing Du,&nbsp;Ning Chen,&nbsp;Mengya Gao,&nbsp;Na Wang,&nbsp;Dongli Qi,&nbsp;Wei Bai,&nbsp;Jianxin Yin,&nbsp;Fengwei Dong,&nbsp;Tianshi Li,&nbsp;Xiaohu Ge","doi":"10.1002/jex2.70009","DOIUrl":"10.1002/jex2.70009","url":null,"abstract":"<p>Exosomes are cell-derived nanovesicles that play a crucial role in intercellular communication, presenting promising potential as biomarkers and therapeutic agents. Bovine milk exosomes (MK-Exo) show production scalability and cost-effectiveness, offering distinct advantages over cell-derived exosomes. However, exosome storage and transportation are challenging owing to their unstable nature, necessitating preservation at ultralow temperatures. Research findings suggest that freeze-drying could provide a viable solution; however, different sources of exosomes may require specific protocols. In this study, we aimed to successfully isolate high-purity MK-Exo and develop a specialized freeze-drying and lyophilization method for improved long-term preservation of MK-Exo. Specifically, the stability of the lyophilized MK-Exo was evaluated using storage stability tests. Notably, lyophilized MK-Exo remained stable for at least 3 months under high temperature of 50°C and for at least 24 months under low temperatures of 2°C–8°C, preserving their physicochemical properties and biological activity. Conclusively, these findings provide a potential solution for ambient-temperature transportation of MK-Exo, facilitating their industrial-scale production.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hepatocyte-derived extracellular vesicles regulate liver regeneration through a negative feedback mechanism 肝细胞源性细胞外囊泡通过负反馈机制调节肝脏再生
Journal of extracellular biology Pub Date : 2024-11-15 DOI: 10.1002/jex2.70023
Mina McGinn, Christopher Rabender, Ross Mikkelsen, Vasily Yakovlev
{"title":"Hepatocyte-derived extracellular vesicles regulate liver regeneration through a negative feedback mechanism","authors":"Mina McGinn,&nbsp;Christopher Rabender,&nbsp;Ross Mikkelsen,&nbsp;Vasily Yakovlev","doi":"10.1002/jex2.70023","DOIUrl":"10.1002/jex2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>While significant progress has been made in understanding various aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver following massive tissue loss or injury of liver remain unknown. As it was previously shown, the loss of liver mass affects putative hepatocyte-specific mitogenic inhibitors in the blood. Although the presence of these putative inhibitors regulating precise liver regeneration has been described in numerous publications, they have never been identified. Extracellular vesicles (EVs) are nano-sized, membrane-limited structures secreted by cells into the extracellular space. Their proposed role is stable intercellular carriers of proteins and RNAs, predominantly micro-RNA, from secreted to recipient cells. Upon uptake by the recipient cells, EVs can significantly modulate their biological functions. In the present study, using in vivo and in vitro models, we demonstrate that hepatocyte proliferation and liver regeneration are regulated by EVs secreted by hepatocytes into the bloodstream. This regulation occurs through a negative feedback mechanism, which explains the precise regeneration of liver tissue after massive damage. We also demonstrate that an essential component of this mechanism is RNA carried by hepatocyte-derived EVs. Our findings open up a new and unexplored area of liver biology regarding the mechanisms involved in the precise regulation of liver regeneration after a massive tissue loss or injury. Further study of this mechanism will have a great influence on the development of new approaches to liver transplantation, various liver pathologies, and hepatic tumors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the ‘dying back’ hypothesis 骨骼肌细胞外囊泡在肌萎缩性脊髓侧索硬化症发病机制中作用的新视角:"死而复生 "假说。
Journal of extracellular biology Pub Date : 2024-11-12 DOI: 10.1002/jex2.70019
Carolina Sbarigia, Sophie Rome, Luciana Dini, Stefano Tacconi
{"title":"New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the ‘dying back’ hypothesis","authors":"Carolina Sbarigia,&nbsp;Sophie Rome,&nbsp;Luciana Dini,&nbsp;Stefano Tacconi","doi":"10.1002/jex2.70019","DOIUrl":"10.1002/jex2.70019","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, and is characterized by muscle weakness, paralysis and ultimately, respiratory failure. The exact causes of ALS are not understood, though it is believed to combine genetic and environmental factors. Until now, it was admitted that motor neurons (MN) in the brain and spinal cord degenerate, leading to muscle weakness and paralysis. However, as ALS symptoms typically begin with muscle weakness or stiffness, a new hypothesis has recently emerged to explain the development of the pathology, that is, the ‘dying back hypothesis’, suggesting that this degeneration starts at the connections between MN and muscles, resulting in the loss of muscle function. Over time, this damage extends along the length of the MN, ultimately affecting their cell bodies in the spinal cord and brain. While the dying back hypothesis provides a potential framework for understanding the progression of ALS, the exact mechanisms underlying the disease remain complex and not fully understood. In this review, we are positioning the role of extracellular vesicles as new actors in ALS development.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Challenging the conventional wisdom: Re-evaluating Smpd3's role in extracellular vesicle biogenesis 挑战传统智慧:重新评估Smpd3在细胞外囊泡生物生成中的作用
Journal of extracellular biology Pub Date : 2024-11-08 DOI: 10.1002/jex2.70015
Marlies Burgelman, Pieter Dujardin, Anthony Willems, Tino Hochepied, Griet Van Imschoot, Elien Van Wonterghem, Lien Van Hoecke, Charysse Vandendriessche, Roosmarijn E. Vandenbroucke
{"title":"Challenging the conventional wisdom: Re-evaluating Smpd3's role in extracellular vesicle biogenesis","authors":"Marlies Burgelman,&nbsp;Pieter Dujardin,&nbsp;Anthony Willems,&nbsp;Tino Hochepied,&nbsp;Griet Van Imschoot,&nbsp;Elien Van Wonterghem,&nbsp;Lien Van Hoecke,&nbsp;Charysse Vandendriessche,&nbsp;Roosmarijn E. Vandenbroucke","doi":"10.1002/jex2.70015","DOIUrl":"10.1002/jex2.70015","url":null,"abstract":"<p>Extracellular vesicles (EVs) are pivotal in intercellular communication, impacting diverse physiological and pathological processes. Current in vitro EV biogenesis studies often utilize pharmacological inhibitors, inducing off-target effects and overlooking cell-specific production nuances. Addressing these limitations, we utilized CRISPR/Cas9 to generate heterozygous full-body and conditional sphingomyelin phosphodiesterase 3 (Smpd3) knockout (KO) transgenic mice. <i>Smpd3</i>, also known as neutral sphingomyelinase 2 (nSMase2), triggers membrane curvature through sphingomyelin hydrolysis to ceramide, thereby influencing exosome release. Intriguingly, <i>Smpd3</i> deficiency demonstrated no impact on EV release both in vitro and in vivo, underscoring its potential cell-type-specific role in EV biogenesis. Notably, bone marrow derived macrophages (BMDMs) did exhibit reduced EV release upon <i>Alix</i> deletion. Our findings open avenues for subsequent inquiries, enriching our knowledge of EV biogenesis and illuminating intercellular communication in health and disease.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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