Giorgia Manni, Marco Gargaro, Doriana Ricciuti, Simona Fontana, Eleonora Padiglioni, Marco Cipolloni, Tommaso Mazza, Jessica Rosati, Alessandra di Veroli, Giulia Mencarelli, Benedetta Pieroni, Estevão Carlos Silva Barcelos, Giulia Scalisi, Francesco Sarnari, Alessandro di Michele, Luisa Pascucci, Francesca de Franco, Teresa Zelante, Cinzia Antognelli, Gabriele Cruciani, Vincenzo Nicola Talesa, Rita Romani, Francesca Fallarino
{"title":"Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model","authors":"Giorgia Manni, Marco Gargaro, Doriana Ricciuti, Simona Fontana, Eleonora Padiglioni, Marco Cipolloni, Tommaso Mazza, Jessica Rosati, Alessandra di Veroli, Giulia Mencarelli, Benedetta Pieroni, Estevão Carlos Silva Barcelos, Giulia Scalisi, Francesco Sarnari, Alessandro di Michele, Luisa Pascucci, Francesca de Franco, Teresa Zelante, Cinzia Antognelli, Gabriele Cruciani, Vincenzo Nicola Talesa, Rita Romani, Francesca Fallarino","doi":"10.1002/jev2.12446","DOIUrl":"10.1002/jev2.12446","url":null,"abstract":"<p>Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored. In this study, we investigated the interaction between highly purified dendritic cell subsets and EVs derived from amniotic fluid stem cell lines (HAFSC-EVs). Our results suggest that HAFSC-EVs are preferentially taken up by conventional dendritic cell type 2 (cDC2) through CD29 receptor-mediated internalization, resulting in a tolerogenic DC phenotype characterized by reduced expression and production of pro-inflammatory mediators. Furthermore, treatment of cDC2 cells with HAFSC-EVs in coculture systems resulted in a higher proportion of T cells expressing the regulatory T cell marker Foxp3 compared to vehicle-treated control cells. Moreover, transfer of HAFSC-EV-treated cDC2s into an EAE mouse model resulted in the suppression of autoimmune responses and clinical improvement. These results suggest that HAFSC-EVs may serve as a promising tool for reprogramming inflammatory cDC2s towards a tolerogenic phenotype and for controlling autoimmune responses in the central nervous system, representing a potential platform for the study of the effects of EVs in DC subsets.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renwei Jing, Leijie Zhang, Ruibin Li, Zhongqiu Yang, Jun Song, Qian Wang, Nan Cao, Gang Han, HaiFang Yin
{"title":"Milk-derived extracellular vesicles functionalized with anti-tumour necrosis factor-α nanobody and anti-microbial peptide alleviate ulcerative colitis in mice","authors":"Renwei Jing, Leijie Zhang, Ruibin Li, Zhongqiu Yang, Jun Song, Qian Wang, Nan Cao, Gang Han, HaiFang Yin","doi":"10.1002/jev2.12462","DOIUrl":"10.1002/jev2.12462","url":null,"abstract":"<p>Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk-derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell-penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti-tumour necrosis factor-α (TNF-α) nanobody (VHHm3F) (EV<sub>VHH</sub>) via TAT significantly reduced tissue TNF-α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EV<sub>LV</sub>), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC-induced depression and anxiety. Collectively, we demonstrated that oral delivery of EV<sub>LV</sub> effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug-loaded orally-administrable EV treatment for other diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suraj Singh Rawat, Anand Kumar Keshri, Naina Arora, Rimanpreet Kaur, Amit Mishra, Rajiv Kumar, Amit Prasad
{"title":"Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model","authors":"Suraj Singh Rawat, Anand Kumar Keshri, Naina Arora, Rimanpreet Kaur, Amit Mishra, Rajiv Kumar, Amit Prasad","doi":"10.1002/jev2.12448","DOIUrl":"10.1002/jev2.12448","url":null,"abstract":"<p>The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like <i>Taenia solium</i>. The cysticerci of <i>T. solium</i> causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150-nm-sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from <i>T. solium</i> larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto-lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV-treated macrophages. Due to this, both macro-autophagy and caspase-linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that <i>T. solium</i> EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV-mediated immune suppression revealed that the EV can protect the mice from DSS-induced colitis and improve colon architecture. These findings shed light on the previously unknown role of <i>T. solium</i> EV and the therapeutic role of their immune suppression potential.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed”","authors":"","doi":"10.1002/jev2.12453","DOIUrl":"10.1002/jev2.12453","url":null,"abstract":"<p>Megan I. Mitchell, Iddo Z. Ben-Dov, Kenny Ye, Christina Liu, Miao Shi, Ali Sadoughi, Chirag Shah, Taha Siddiqui, Aham Okorozo, Martin Gutierrez, Rashmi Unawane, Lisa Biamonte, Kaushal Parikh, Simon Spivack, Olivier Loudig</p><p>In the originally published article, author Kaushal Parikh's name was misspelled. This has been corrected in the online version of the article.</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Burt, Georgia Angelidou, Christopher Nils Mais, Christian Preußer, Timo Glatter, Thomas Heimerl, Rüdiger Groß, Javier Serrania, Gowtham Boosarpu, Elke Pogge von Strandmann, Janis A. Müller, Gert Bange, Anke Becker, Mareike Lehmann, Danny Jonigk, Lavinia Neubert, Hinrich Freitag, Nicole Paczia, Bernd Schmeck, Anna Lena Jung
{"title":"Lipid A in outer membrane vesicles shields bacteria from polymyxins","authors":"Marie Burt, Georgia Angelidou, Christopher Nils Mais, Christian Preußer, Timo Glatter, Thomas Heimerl, Rüdiger Groß, Javier Serrania, Gowtham Boosarpu, Elke Pogge von Strandmann, Janis A. Müller, Gert Bange, Anke Becker, Mareike Lehmann, Danny Jonigk, Lavinia Neubert, Hinrich Freitag, Nicole Paczia, Bernd Schmeck, Anna Lena Jung","doi":"10.1002/jev2.12447","DOIUrl":"10.1002/jev2.12447","url":null,"abstract":"<p>The continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with <i>Klebsiella pneumoniae</i> being a prominent threat. We conducted a comprehensive study on <i>K. pneumoniae</i>’s antibiotic resistance mechanisms, focusing on outer membrane vesicles (OMVs) and polymyxin, a last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. OMVs derived from Polymyxin B (PB)-stressed <i>K. pneumoniae</i> exhibited heightened protective efficacy due to increased vesiculation, compared to OMVs from unstressed <i>Klebsiella</i>. OMVs also shield bacteria from different bacterial families. This was validated ex vivo and in vivo using precision cut lung slices (PCLS) and <i>Galleria mellonella</i>. In all models, OMVs protected <i>K. pneumoniae</i> from PB and reduced the associated stress response on protein level. We observed significant changes in the lipid composition of OMVs upon PB treatment, affecting their binding capacity to PB. The altered binding capacity of single OMVs from PB stressed <i>K. pneumoniae</i> could be linked to a reduction in the lipid A amount of their released vesicles. Although the amount of lipid A per vesicle is reduced, the overall increase in the number of vesicles results in an increased protection because the sum of lipid A and therefore PB binding sites have increased. This unravels the mechanism of the altered PB protective efficacy of OMVs from PB stressed <i>K. pneumoniae</i> compared to control OMVs. The lipid A-dependent protective effect against PB was confirmed in vitro using artificial vesicles. Moreover, artificial vesicles successfully protected <i>Klebsiella</i> from PB ex vivo and in vivo. The findings indicate that OMVs act as protective shields for bacteria by binding to polymyxins, effectively serving as decoys and preventing antibiotic interaction with the cell surface. Our findings provide valuable insights into the mechanisms underlying antibiotic cross-protection and offer potential avenues for the development of novel therapeutic interventions to address the escalating threat of multidrug-resistant bacterial infections.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Cell-engineered virus-mimetic nanovesicles for vaccination against enveloped viruses”","authors":"","doi":"10.1002/jev2.12452","DOIUrl":"10.1002/jev2.12452","url":null,"abstract":"<p>Han, C., Kim, S., Seo, Y., Lim, M., Kwon, Y., Yi, J., Oh, S.-I., Kang, M., Jeon, S. G., & Park, J. (2024). Cell-engineered virus-mimetic nanovesicles for vaccination against enveloped viruses. Journal of Extracellular Vesicles, 13, e12438. https://doi.org/10.1002/jev2.12438</p><p>In the originally published article, the acknowledgements section was incorrect. The correct text is as follows:</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nhan Vo, Chau Tran, Nam H. B. Tran, Nhat T. Nguyen, Thieu Nguyen, Duyen T. K. Ho, Diem D. N. Nguyen, Tran Pham, Tien Anh Nguyen, Hoa T. N. Phan, Hoai-Nghia Nguyen, Lan N. Tu
{"title":"A novel multi-stage enrichment workflow and comprehensive characterization for HEK293F-derived extracellular vesicles","authors":"Nhan Vo, Chau Tran, Nam H. B. Tran, Nhat T. Nguyen, Thieu Nguyen, Duyen T. K. Ho, Diem D. N. Nguyen, Tran Pham, Tien Anh Nguyen, Hoa T. N. Phan, Hoai-Nghia Nguyen, Lan N. Tu","doi":"10.1002/jev2.12454","DOIUrl":"10.1002/jev2.12454","url":null,"abstract":"<p>Extracellular vesicles (EVs) are emerging as a promising drug delivery vehicle as they are biocompatible and capable of targeted delivery. However, clinical translation of EVs remains challenging due to the lack of standardized and scalable manufacturing protocols to consistently isolate small EVs (sEVs) with both high yield and high purity. The heterogenous nature of sEVs leading to unknown composition of biocargos causes further pushback due to safety concerns. In order to address these issues, we developed a robust quality-controlled multi-stage process to produce and isolate sEVs from human embryonic kidney HEK293F cells. We then compared different 2-step and 3-step workflows for eliminating protein impurities and cell-free nucleic acids to meet acceptable limits of regulatory authorities. Our results showed that sEV production was maximized when HEK293F cells were grown at high-density stationary phase in semi-continuous culture. The novel 3-step workflow combining tangential flow filtration, sucrose-cushion ultracentrifugation and bind-elute size-exclusion chromatography outperformed other methods in sEV purity while still preserved high yield and particle integrity. The purified HEK293F-derived sEVs were thoroughly characterized for identity including sub-population analysis, content profiling including proteomics and miRNA sequencing, and demonstrated excellent preclinical safety profile in both in-vitro and in-vivo testing. Our rigorous enrichment workflow and comprehensive characterization will help advance the development of EVs, particularly HEK293F-derived sEVs, to be safe and reliable drug carriers for therapeutic applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clorinda Fusco, Giusy De Rosa, Ilaria Spatocco, Elisabetta Vitiello, Claudio Procaccini, Chiara Frigè, Valeria Pellegrini, Rosalba La Grotta, Roberto Furlan, Giuseppe Matarese, Francesco Prattichizzo, Paola de Candia
{"title":"Extracellular vesicles as human therapeutics: A scoping review of the literature","authors":"Clorinda Fusco, Giusy De Rosa, Ilaria Spatocco, Elisabetta Vitiello, Claudio Procaccini, Chiara Frigè, Valeria Pellegrini, Rosalba La Grotta, Roberto Furlan, Giuseppe Matarese, Francesco Prattichizzo, Paola de Candia","doi":"10.1002/jev2.12433","DOIUrl":"10.1002/jev2.12433","url":null,"abstract":"<p>Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans.</p><p>The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well-designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches”","authors":"","doi":"10.1002/jev2.12451","DOIUrl":"10.1002/jev2.12451","url":null,"abstract":"<p>Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrügger, U., Falcon-Perez, J. M., Fu, Q.-L., Hill, A. F., Lenassi, M., Lim, S. K., Mahoney, M. G., Mohanty, S., Möller, A., Nieuwland, R., … Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. <i>Journal of Extracellular Vesicles</i>, 13, e12404. https://doi.org/10.1002/jev2.12404</p><p>In the originally published article, Gisela D'Angelo was omitted from the MISEV Consortium. They have been added to the online version of the article. We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hernán González-King, Patricia G. Rodrigues, Tamsin Albery, Benyapa Tangruksa, Ramya Gurrapu, Andreia M. Silva, Gentian Musa, Dominika Kardasz, Kai Liu, Bengt Kull, Karin Åvall, Katarina Rydén-Markinhuhta, Tania Incitti, Nitin Sharma, Cecilia Graneli, Hadi Valadi, Kasparas Petkevicius, Miguel Carracedo, Sandra Tejedor, Alena Ivanova, Sepideh Heydarkhan-Hagvall, Phillipe Menasché, Jane Synnergren, Niek Dekker, Qing-Dong Wang, Karin Jennbacken
{"title":"Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair: Superiority of embryonic stem cells","authors":"Hernán González-King, Patricia G. Rodrigues, Tamsin Albery, Benyapa Tangruksa, Ramya Gurrapu, Andreia M. Silva, Gentian Musa, Dominika Kardasz, Kai Liu, Bengt Kull, Karin Åvall, Katarina Rydén-Markinhuhta, Tania Incitti, Nitin Sharma, Cecilia Graneli, Hadi Valadi, Kasparas Petkevicius, Miguel Carracedo, Sandra Tejedor, Alena Ivanova, Sepideh Heydarkhan-Hagvall, Phillipe Menasché, Jane Synnergren, Niek Dekker, Qing-Dong Wang, Karin Jennbacken","doi":"10.1002/jev2.12445","DOIUrl":"https://doi.org/10.1002/jev2.12445","url":null,"abstract":"<p>Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.12445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}