Adityas Purnianto, Celeste Mawal, Mitali M. Kulkarni, Huaqi Su, Tiana F. Koukoulis, Patricia Wongsodirdjo, Ya Hui Hung, Scott Ayton, Ashley I. Bush, Kevin J. Barnham, Laura J. Vella
{"title":"Small extracellular vesicles contain metals and transfer metal intercellularly","authors":"Adityas Purnianto, Celeste Mawal, Mitali M. Kulkarni, Huaqi Su, Tiana F. Koukoulis, Patricia Wongsodirdjo, Ya Hui Hung, Scott Ayton, Ashley I. Bush, Kevin J. Barnham, Laura J. Vella","doi":"10.1002/jex2.70012","DOIUrl":"https://doi.org/10.1002/jex2.70012","url":null,"abstract":"<p>Cells have developed a highly regulated system for the uptake, transport, utilization, storage, and export of metals, ensuring the maintenance of cellular homeostasis. Small extracellular vesicles (sEVs) function as a mechanism through which a cell can export its cargo and transfer it to recipient cells. However, in contrast to the other molecular cargo associated with sEVs, the metal content of sEVs is not well characterized. To address this gap in knowledge, we measured the levels of nine essential metals (copper, iron, zinc, manganese, magnesium, potassium, calcium, chromium, cobalt) and six non-essential metals (nickel, rubidium, titanium, aluminium, lithium, lead) in sEVs originating from multiple in vitro and <i>ex vivo</i> sources. Our findings reveal that, beyond containing redox-active essential metals and those involved in redox reactions, sEVs also exhibit the capability to export and transfer non-physiological, potentially toxic metals.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435605","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}
Joseph Brealey, Rebecca Lees, Robert Tempest, Alice Law, Sonia Guarnerio, Rawan Maani, Soozana Puvanenthiran, Nick Peake, Ryan Pink, Ben Peacock
{"title":"Shining a light on fluorescent EV dyes: Evaluating efficacy, specificity and suitability by nano-flow cytometry","authors":"Joseph Brealey, Rebecca Lees, Robert Tempest, Alice Law, Sonia Guarnerio, Rawan Maani, Soozana Puvanenthiran, Nick Peake, Ryan Pink, Ben Peacock","doi":"10.1002/jex2.70006","DOIUrl":"https://doi.org/10.1002/jex2.70006","url":null,"abstract":"<p>Extracellular vesicles (EVs) are mediators of intercellular communication, recently recognised for their clinical applications. Accurate characterisation and quantification of EVs are critical for understanding of their function and clinical relevance. Many platforms utilise fluorescence for EV characterisation, frequently labelling surface proteins to identify EVs. The heterogeneity of EVs and the lack of a universal protein marker encourages the use of generic EV labelling methods, including membrane labelling. Using nano-flow cytometry, we evaluated six membrane dyes, including MemGlow and CellMask. Evaluation criteria included EV labelling efficacy, non-specific labelling of very low-density lipoproteins (VLDLs), brightness and dye aggregation. Significant variation was observed in dye performance, with certain dyes showing poor EV labelling efficacy or high affinity to VLDLs. Importantly, several promising candidates were identified for further investigation. Overall, this study highlights the importance of selecting appropriate membrane dyes for EV staining tailored to the aims of the study and the EV origin. MemGlow and CellMask proved favourable, allowing bright, sensitive staining of EV membranes with minimal aggregation. However, MemGlow showed an affinity to VLDLs, and CellMask requires additional sample handling for optimal labelling. These results contribute to deepening our understanding of EV membrane dyes, allowing for better dye selection and EV identification in future studies.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429931","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}
{"title":"Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach","authors":"Ofir Bar, Angel Porgador, Tomer Cooks","doi":"10.1002/jex2.70011","DOIUrl":"https://doi.org/10.1002/jex2.70011","url":null,"abstract":"<p>Cancer therapy is a dynamically evolving field, witnessing the emergence of innovative approaches that offer a promising outlook for patients grappling with persistent disease. Within the realm of therapeutic exploration, chimeric antigen receptor (CAR) T cells as well as CAR NK cells, have surfaced as novel approaches, each possessing unique attributes and transformative potential. Immune cells engineered to express CARs recognizing tumour-specific antigens, have shown remarkable promise in treating terminal cancers by combining the precision of antibody specificity with the potent cytotoxic function of T cells. However, their application in solid tumours is still in its nascent stages, presenting unique major challenges. On the same note, CAR NK cells offer a distinct immunotherapeutic approach, utilizing CARs on NK cells, providing advantages in safety, manufacturing simplicity, and a broader scope for cancer treatment. Extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to carry crucial biomarkers and biologically active molecules, serving as vital messengers in the intercellular communication network. In the context of cancer, the therapeutic potential of EVs lies in delivering tumour-suppressing proteins, nucleic acid components, or targeting drugs with precision, thereby redefining the paradigm of precision medicine. The fusion of CAR technology with the capabilities of EVs has given rise to a new therapeutic frontier. CAR T EVs and CAR NK EVs, leveraging the power of EVs, have the potential to alleviate challenges associated with live-cell therapies. EVs are suggested to reduce the side effects linked to CAR T cell therapy and hold the potential to revolutionize the penetrance in solid tumours. EVs act as carriers of pro-apoptotic molecules and RNA components, enhancing immune responses and thereby expanding their therapeutic potential. In this review article, we navigate dynamic landscapes, with our objective being to evaluate comparative efficacy, safety profiles, manufacturing complexities, and clinical applicability.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324673","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}
Miriam Anfaiha-Sanchez, Aranzazu Santiago-Hernandez, Juan Antonio Lopez, Nerea Lago-Baameiro, Maria Pardo, Ariadna Martin-Blazquez, Jesus Vazquez, Gema Ruiz-Hurtado, Maria G. Barderas, Julian Segura, Luis M. Ruilope, Marta Martin-Lorenzo, Gloria Alvarez-Llamas
{"title":"Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease","authors":"Miriam Anfaiha-Sanchez, Aranzazu Santiago-Hernandez, Juan Antonio Lopez, Nerea Lago-Baameiro, Maria Pardo, Ariadna Martin-Blazquez, Jesus Vazquez, Gema Ruiz-Hurtado, Maria G. Barderas, Julian Segura, Luis M. Ruilope, Marta Martin-Lorenzo, Gloria Alvarez-Llamas","doi":"10.1002/jex2.170","DOIUrl":"https://doi.org/10.1002/jex2.170","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin-to-creatinine ratio (ACR) 30 mg/g is a cut-off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR > 60 mL/min/1.73 m<sup>2</sup> are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher-risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non-invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hypertensive patients were classified in control group (C) with ACR < 10 mg/g, and high-normal group (HN) with ACR 10–30 mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC-MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long-chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alterations in the EV-mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244874","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}
Dimitrios Pollalis, Gopa Kumar Gopinadhan Nair, Justin Leung, Clarisa Marie Bloemhof, Jeffrey K. Bailey, Britney O. Pennington, Kaitlin R. Kelly, Amir I. Khan, Ashley K. Yeh, Kartik S. Sundaram, Dennis O. Clegg, Chen-Ching Peng, Liya Xu, Constantin Georgescu, Jonathan D. Wren, Sun Young Lee
{"title":"Dynamics of microRNA secreted via extracellular vesicles during the maturation of embryonic stem cell-derived retinal pigment epithelium","authors":"Dimitrios Pollalis, Gopa Kumar Gopinadhan Nair, Justin Leung, Clarisa Marie Bloemhof, Jeffrey K. Bailey, Britney O. Pennington, Kaitlin R. Kelly, Amir I. Khan, Ashley K. Yeh, Kartik S. Sundaram, Dennis O. Clegg, Chen-Ching Peng, Liya Xu, Constantin Georgescu, Jonathan D. Wren, Sun Young Lee","doi":"10.1002/jex2.70001","DOIUrl":"https://doi.org/10.1002/jex2.70001","url":null,"abstract":"<p>Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE-secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV-secreting cell and understanding the biological cargo of EVs to develop EV-based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); <i>early</i>-<i>stage</i> hESC-RPE (20–21 days in culture), <i>mid</i>-<i>stage</i> hESC-RPE (30–31 days in culture) and <i>late</i>-<i>stage</i> hESC-RPE (60–61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV-based intraocular therapeutics utilizing RPE-secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230999","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}
Shimian Qu, Hannah M. Nelson, Xiao Liu, Yu Wang, Elizabeth M. Semler, Danielle L. Michell, Clark Massick, Jeffrey L. Franklin, John Karijolich, Alissa M. Weaver, Robert J. Coffey, Qi Liu, Kasey C. Vickers, James G. Patton
{"title":"5-Fluorouracil treatment represses pseudouridine-containing miRNA export into extracellular vesicles","authors":"Shimian Qu, Hannah M. Nelson, Xiao Liu, Yu Wang, Elizabeth M. Semler, Danielle L. Michell, Clark Massick, Jeffrey L. Franklin, John Karijolich, Alissa M. Weaver, Robert J. Coffey, Qi Liu, Kasey C. Vickers, James G. Patton","doi":"10.1002/jex2.70010","DOIUrl":"https://doi.org/10.1002/jex2.70010","url":null,"abstract":"<p>5-Fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5-FU on post-transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell-cell communication. We found that treatment of colorectal cancer (CRC) cells with 5-FU represses sEV export of miRNA and snRNA-derived RNAs, but promotes export of snoRNA-derived RNAs. Strikingly, 5-FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5-FU exposure led to increased levels of cellular small RNAs containing a variety of methyl-modified bases. These unexpected findings show that 5-FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230998","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}
Géraldine C. Genard, Luca Tirinato, Francesca Pagliari, Jessica Da Silva, Alessandro Giammona, Fatema Alquraish, Maria Parra Reyes, Marie Bordas, Maria Grazia Marafioti, Simone Di Franco, Jeannette Janssen, Daniel Garcia-Calderón, Rachel Hanley, Clelia Nistico, Yoshinori Fukasawa, Torsten Müller, Jeroen Krijgsveld, Matilde Todaro, Francesco Saverio Costanzo, Giorgio Stassi, Michelle Nessling, Karsten Richter, Kendra K. Maass, Carlo Liberale, Joao Seco
{"title":"Lipid droplets and small extracellular vesicles: More than two independent entities","authors":"Géraldine C. Genard, Luca Tirinato, Francesca Pagliari, Jessica Da Silva, Alessandro Giammona, Fatema Alquraish, Maria Parra Reyes, Marie Bordas, Maria Grazia Marafioti, Simone Di Franco, Jeannette Janssen, Daniel Garcia-Calderón, Rachel Hanley, Clelia Nistico, Yoshinori Fukasawa, Torsten Müller, Jeroen Krijgsveld, Matilde Todaro, Francesco Saverio Costanzo, Giorgio Stassi, Michelle Nessling, Karsten Richter, Kendra K. Maass, Carlo Liberale, Joao Seco","doi":"10.1002/jex2.162","DOIUrl":"https://doi.org/10.1002/jex2.162","url":null,"abstract":"<p>Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell–cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid-interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine-tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160293","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}
Jose G. Marchan-Alvarez, Loes Teeuwen, Doste R. Mamand, Susanne Gabrielsson, Klas Blomgren, Oscar P. B. Wiklander, Phillip T. Newton
{"title":"A protocol to differentiate the chondrogenic ATDC5 cell-line for the collection of chondrocyte-derived extracellular vesicles","authors":"Jose G. Marchan-Alvarez, Loes Teeuwen, Doste R. Mamand, Susanne Gabrielsson, Klas Blomgren, Oscar P. B. Wiklander, Phillip T. Newton","doi":"10.1002/jex2.70004","DOIUrl":"10.1002/jex2.70004","url":null,"abstract":"<p>Skeletal growth and fracture healing rely on the mineralization of cartilage in a process called endochondral ossification. Chondrocytes firstly synthesize and then modify cartilage by the release of a wide range of particles into their extracellular space. Extracellular vesicles (EVs) are one type of such particles, but their roles in endochondral ossification are yet to be fully understood. It remains a challenge to obtain representative populations of chondrocyte-derived EVs, owing to difficulties both in preserving the function of primary chondrocytes in culture and in applying the serum-free conditions required for EV production. Here, we used the ATDC5 cell-line to recover chondrocyte-derived EVs from early- and late-differentiation stages, representing chondrocytes before and during cartilage mineralization. After screening different culture conditions, our data indicate that a serum-free Opti-MEM-based culture medium preserves chondrocyte identity and function, matrix mineralization and cell viability. We subsequently scaled-up production and isolated EVs from conditioned medium by size-exclusion chromatography. The obtained chondrocyte-derived EVs had typical ultrastructure and expression of classical EV markers, at quantities suitable for downstream experiments. Importantly, chondrocyte-derived EVs from late-differentiation stages had elevated levels of alkaline phosphatase activity. Hence, we established a method to obtain functional chondrocyte-derived EVs before and during cartilage mineralization that may aid the further understanding of their roles in endochondral bone growth and fracture healing.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141939","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}
Roksan Franko, Marcia de Almeida Monteiro Melo Ferraz
{"title":"Exploring the potential of in vitro extracellular vesicle generation in reproductive biology","authors":"Roksan Franko, Marcia de Almeida Monteiro Melo Ferraz","doi":"10.1002/jex2.70007","DOIUrl":"10.1002/jex2.70007","url":null,"abstract":"<p>The interest in the growing field of extracellular vesicle (EV) research highlights their significance in intercellular signalling and the selective transfer of biological information between donor and recipient cells. EV studies have provided valuable insights into intercellular communication mechanisms, signal identification and their involvement in disease states, offering potential avenues for manipulating pathological conditions, detecting biomarkers and developing drug-delivery systems. While our understanding of EV functions in reproductive tissues has significantly progressed, exploring their potential as biomarkers for infertility, therapeutic interventions and enhancements in assisted reproductive technologies remains to be investigated. This knowledge gap stems partly from the difficulties associated with large-scale EV production relevant to clinical applications. Most existing studies on EV production rely on conventional 2D cell culture systems, characterized by suboptimal EV yields and a failure to replicate in vivo conditions. This results in the generation of EVs that differ from their in vivo counterparts. Hence, this review firstly delves into the importance of EVs in reproduction to then expand on current techniques for in vitro EV production, specifically examining diverse methods of culture and the potential of bioengineering technologies to establish innovative systems for enhanced EV production.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141940","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}
Aliona Wöhler, Sabine K. Gries, Rebekka J. S. Salzmann, Christina Krötz, Bingduo Wang, Paula Müller, Angelina Klein, Ingo G. H. Schmidt-Wolf, Sebastian Schaaf, Robert Schwab, Veronika Lukacs-Kornek, Arnulf G. Willms, Miroslaw T. Kornek
{"title":"Monocyte derived large extracellular vesicles in polytrauma","authors":"Aliona Wöhler, Sabine K. Gries, Rebekka J. S. Salzmann, Christina Krötz, Bingduo Wang, Paula Müller, Angelina Klein, Ingo G. H. Schmidt-Wolf, Sebastian Schaaf, Robert Schwab, Veronika Lukacs-Kornek, Arnulf G. Willms, Miroslaw T. Kornek","doi":"10.1002/jex2.70005","DOIUrl":"10.1002/jex2.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Despite significant progress in the medical field, there is still a pressing need for minimal-invasive tools to assist with decision-making, especially in cases of polytrauma. Our team explored the potential of serum-derived large extracellular vesicles, so called microparticles/microvesicles/ectosomes, to serve as a supportive tool in decision-making in polytrauma situations. We focused on whether monocyte derived large EVs may differentiate between polytrauma patients with internal organ injury (ISS > 15) and those without. Thus, we compared our EV data to soluble biomarkers such as tumour necrosis factor alpha (TNF alpha) and Interleukin-8 (IL-8). From the blood of 25 healthy and 26 patients with polytrauma large EVs were isolated, purified, and characterized. TNF alpha and IL-8 levels were quantified. We found that levels of these monocyte derived large EVs were significantly higher in polytrauma patients with internal organ damage and correlated with the ISS. Interestingly, we also observed a decline in AnnV<sup>+</sup>CD14<sup>+</sup> large EVs during normal recovery after trauma. Thus, inflammatory serological markers as TNF alpha and as IL-8 demonstrated an inability to discriminate between polytrauma patients with or without internal organ damage, such as spleen, kidney, or liver lacerations/ruptures. However, TNF and IL-8 levels were elevated in polytrauma cases overall when contrasted with healthy non-traumatic controls. These findings suggest that delving deeper into the potential of AnnV<sup>+</sup> large EVs derived from monocytes could highly beneficial in the managment of polytrauma, potentially surpassing the efficacy of commonly used serum markers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121272","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}