Extracellular vesicle最新文献_第7页

Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma 靶向MYC的工程外泌体逆转前膜-间充质转化并延长胶质母细胞瘤的生存期

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100014

Amanda R. Haltom , Wafa E. Hassen , Janine Hensel , Jiha Kim , Hikaru Sugimoto , Bingrui Li , Kathleen M. McAndrews , Meagan R. Conner , Michelle L. Kirtley , Xin Luo , Bingqing Xie , Olga V. Volpert , Susan Olalekan , Natalia Maltsev , Anindita Basu , Valerie S. LeBleu , Raghu Kalluri

{"title":"Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma","authors":"Amanda R. Haltom , Wafa E. Hassen , Janine Hensel , Jiha Kim , Hikaru Sugimoto , Bingrui Li , Kathleen M. McAndrews , Meagan R. Conner , Michelle L. Kirtley , Xin Luo , Bingqing Xie , Olga V. Volpert , Susan Olalekan , Natalia Maltsev , Anindita Basu , Valerie S. LeBleu , Raghu Kalluri","doi":"10.1016/j.vesic.2022.100014","DOIUrl":"10.1016/j.vesic.2022.100014","url":null,"abstract":"<div><p>Dysregulated Myc signaling is a key oncogenic pathway in glioblastoma multiforme (GBM). Yet, effective therapeutic targeting of Myc continues to be challenging. Here, we demonstrate that exosomes generated from human bone marrow mesenchymal stem cells (MSCs) engineered to encapsulate siRNAs targeting Myc (iExo-Myc) localize to orthotopic GBM tumors in mice. Treatment of late stage GBM tumors with iExo-Myc inhibits proliferation and angiogenesis, suppresses tumor growth, and extends survival. Transcriptional profiling of tumors reveals that the mesenchymal transition and estrogen receptor signaling pathways are impacted by Myc inhibition. Single nuclei RNA sequencing (snRNA-seq) shows that iExo-Myc treatment induces transcriptional repression of multiple growth factor and interleukin signaling pathways, triggering a mesenchymal to proneural transition and shifting the cellular landscape of the tumor. These data confirm that Myc is an effective anti-glioma target and that iExo-Myc offers a feasible, readily translational strategy to inhibit challenging oncogene targets for the treatment of brain tumors.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100014"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373511/pdf/nihms-1913722.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9893951","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: 5

Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung 可吸入外泌体作为肺mRNA和蛋白质药物载体优于脂质体

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100002

Kristen D. Popowski , Blanca López de Juan Abad , Arianna George , Dylan Silkstone , Elizabeth Belcher , Jaewook Chung , Asma Ghodsi , Halle Lutz , Jada Davenport , Mallory Flanagan , Jorge Piedrahita , Phuong-Uyen C. Dinh , Ke Cheng

{"title":"Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung","authors":"Kristen D. Popowski , Blanca López de Juan Abad , Arianna George , Dylan Silkstone , Elizabeth Belcher , Jaewook Chung , Asma Ghodsi , Halle Lutz , Jada Davenport , Mallory Flanagan , Jorge Piedrahita , Phuong-Uyen C. Dinh , Ke Cheng","doi":"10.1016/j.vesic.2022.100002","DOIUrl":"10.1016/j.vesic.2022.100002","url":null,"abstract":"<div><p>Respiratory diseases are among the leading causes of morbidity and mortality worldwide, coupled with the ongoing coronavirus disease 2019 (COVID-19) pandemic. mRNA lipid nanoparticle (LNP) vaccines have been developed, but their intramuscular delivery limits pulmonary bioavailability. Inhalation of nanoparticle therapeutics offers localized drug delivery that minimizes off targeted adverse effects and has greater patient compliance. However, LNP platforms require extensive reformulation for inhaled delivery. Lung-derived extracellular vesicles (Lung-Exo) offer a biological nanoparticle alternative that is naturally optimized for mRNA translation and delivery to pulmonary cells. We compared the biodistribution of Lung-Exo against commercially standard biological extracellular vesicles (HEK-Exo) and LNPs (Lipo), where Lung-Exo exhibited superior mRNA and protein cargo distribution to and retention in the bronchioles and parenchyma following nebulization administration. This suggests that inhaled Lung-Exo can deliver mRNA and protein drugs with enhanced pulmonary bioavailability and therapeutic efficacy.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287060","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: 21

Cell-derived nanovesicles prepared by membrane extrusion are good substitutes for natural extracellular vesicles 通过膜挤压法制备的细胞源性纳米囊泡是天然细胞外囊泡的良好替代品

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100004

Yi Wen , Qin Fu , Ashley Soliwoda , Sheng Zhang , Mingfeng Zheng , Wenjun Mao , Yuan Wan

{"title":"Cell-derived nanovesicles prepared by membrane extrusion are good substitutes for natural extracellular vesicles","authors":"Yi Wen , Qin Fu , Ashley Soliwoda , Sheng Zhang , Mingfeng Zheng , Wenjun Mao , Yuan Wan","doi":"10.1016/j.vesic.2022.100004","DOIUrl":"10.1016/j.vesic.2022.100004","url":null,"abstract":"<div><p>Extracellular vesicles (EV) as drug delivery nanocarriers are under intense investigation. Although clinical-grade EVs have been produced on a large-scale, low yield and high production costs of natural EVs (nEV) limit the relevant industrial translation. Recent studies show that mechanical extrusion of cells can generate nEV-like cell-derived nanovesicles (CNV) which can also be used as drug nanocarriers. Moreover, in comparison with nEVs, CNVs have similar physicochemical properties. Nevertheless, a comprehensive comparison of cargo between nEVs and CNVs has not been investigated yet. Therefore, the aim of this study is to profile and compare CNVs to nEVs. Our results show that no significant difference was found in size, morphology, and classical markers between nEVs and CNVs derived from MDA-MB-231 cells. Protein sequencing data reveals the similarity of membrane proteins between the two groups was <span><math><mo>∼</mo></math></span>71%, while it was <span><math><mo>∼</mo></math></span>21% when pertaining to total protein cargo. Notably, a high similarity of membrane proteins was also found between nEVs and CNVs derived from eight additional cancer cell lines. Moreover, analysis of the top 1000 small RNAs with RNA sequencing showed a <span><math><mo>∼</mo></math></span>65% similarity between the two groups. Altogether, we infer from the high similarity of membrane proteins and small RNA cargo that CNVs can be a good substitute for nEVs. In brief, our findings support previous studies with a notion that CNVs yield comparable performance with nEVs and could pave the way for clinical implementation of CNV-based therapeutics in the future.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/95/nihms-1859360.PMC9794200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509824","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: 24

Sucrose-based cryoprotective storage of extracellular vesicles 以蔗糖为基础的细胞外囊泡冷冻保护储存

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100016

Sierra A. Walker , Irina Davidovich , Yubo Yang , Andrew Lai , Jenifer Pendiuk Goncalves , Vatsal Deliwala , Sara Busatto , Shane Shapiro , Na’ama Koifman , Carlos Salomon , Yeshayahu Talmon , Joy Wolfram

{"title":"Sucrose-based cryoprotective storage of extracellular vesicles","authors":"Sierra A. Walker , Irina Davidovich , Yubo Yang , Andrew Lai , Jenifer Pendiuk Goncalves , Vatsal Deliwala , Sara Busatto , Shane Shapiro , Na’ama Koifman , Carlos Salomon , Yeshayahu Talmon , Joy Wolfram","doi":"10.1016/j.vesic.2022.100016","DOIUrl":"10.1016/j.vesic.2022.100016","url":null,"abstract":"<div><p>Advancements in extracellular vesicle (EV) studies necessitate the development of optimized storage conditions to ensure preservation of physical and biochemical characteristics. In this study, the most common buffer for EV storage (phosphate-buffered saline/PBS) was compared to a cryoprotective 5% sucrose solution. The size distribution and concentration of EVs from two different sources changed to a greater extent after −80 °C storage in PBS compared to the sucrose solution. Additionally, molecular surface protrusions and transmembrane proteins were more prevalent in EVs stored in the sucrose solution compared to those stored in PBS. This study demonstrates, for the first time, that distinct ring-like molecular complexes and cristae-like folded membranous structures are visible upon EV degradation. Taken together, the size, concentration, molecular surface extensions, and transmembrane proteins of EVs varied substantially based on the buffer used for −80 °C storage, suggesting that biocompatible cryoprotectants, such as sucrose, should be considered for EV studies.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000117/pdfft?md5=86b94a603c3bfe47ab1d92a96499da88&pid=1-s2.0-S2773041722000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42655161","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: 7

Greasing wheels of cell-free therapies for cardiovascular diseases: Integrated devices of exosomes/exosome-like nanovectors with bioinspired materials 心血管疾病的无细胞治疗:外泌体/类外泌体纳米载体与生物启发材料的集成装置

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100010

Xuerui Chen , Liyun Zhu , Jianyun Liu , Yi Lu , Longlu Pan , Junjie Xiao

{"title":"Greasing wheels of cell-free therapies for cardiovascular diseases: Integrated devices of exosomes/exosome-like nanovectors with bioinspired materials","authors":"Xuerui Chen , Liyun Zhu , Jianyun Liu , Yi Lu , Longlu Pan , Junjie Xiao","doi":"10.1016/j.vesic.2022.100010","DOIUrl":"10.1016/j.vesic.2022.100010","url":null,"abstract":"<div><p>Mortality and morbidity of cardiovascular diseases (CVDs) including ischemic heart disease (IHD) and heart failure (HF) are arising worldwide. Once cardiomyocyte is impaired, it is challenging to regenerate which is largely limited by the irreversibility of cell cycle after birth. Emergent approaches in regenerative medicine head toward the application of extracellular vesicles (EVs) such as exosomes in next-generation cell-free treatment strategies for CVDs, attributed to their repair promotion. However, naked exosomes undergo major obstacles of high clearance by the mononuclear phagocyte system and transient retention of exosomes in transplanted areas, eventually failing in the endogenous repair. Strategies optimizing matrix materials to release exosomes in a targeted, sustained and minimally invasive manner will pave the way for empowering cardiac repair and regeneration. In this review, we extensively summarize the integrated devices of exosome or exosome-like nanovectors with biomaterials for treating CVDs. Furthermore, we provide recommendations on how combinations of exosomes/ biomaterials (e.g. hydrogels, stents, cell sheets, cardiac patches, microneedles, spray and 3D tissue matrix) increase the success rate of cell-free therapies which will boost cardiac repair and regeneration in the clinical settings of CVDs.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000051/pdfft?md5=83d800a9d9334377c88c5c73fb555965&pid=1-s2.0-S2773041722000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48288316","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: 3

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure 单期丰坦法幼羊模型血清源性细胞外囊泡mirna的计算分析

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100013

Hyun-Ji Park , John M. Kelly , Jessica R. Hoffman , Felipe Takaesu , William Schwartzman , Anudari Ulziibayar , Takahiro Kitsuka , Eric Heuer , Asigul Yimit , Raphael Malbrue , Cole Anderson , Adrienne Morrison , Aymen Naguib , Christopher Mckee , Andrew Harrison , Brian Boe , Aimee Armstrong , Arash Salavitabar , Andrew Yates , Toshiharu Shinoka , Michael E. Davis

{"title":"Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure","authors":"Hyun-Ji Park , John M. Kelly , Jessica R. Hoffman , Felipe Takaesu , William Schwartzman , Anudari Ulziibayar , Takahiro Kitsuka , Eric Heuer , Asigul Yimit , Raphael Malbrue , Cole Anderson , Adrienne Morrison , Aymen Naguib , Christopher Mckee , Andrew Harrison , Brian Boe , Aimee Armstrong , Arash Salavitabar , Andrew Yates , Toshiharu Shinoka , Michael E. Davis","doi":"10.1016/j.vesic.2022.100013","DOIUrl":"10.1016/j.vesic.2022.100013","url":null,"abstract":"<div><p>Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10757510","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: 1

Complex RNA world in small extracellular vesicles for liquid biopsy in cancer management 细胞外小泡液体活检在癌症治疗中的复杂RNA世界

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100015

Shuhong Wang , Yusheng Lin , Yishi Zhang , Xiaofu Qiu , Yunlong Pan , Sai-Ching Jim Yeung , Hao Zhang

{"title":"Complex RNA world in small extracellular vesicles for liquid biopsy in cancer management","authors":"Shuhong Wang , Yusheng Lin , Yishi Zhang , Xiaofu Qiu , Yunlong Pan , Sai-Ching Jim Yeung , Hao Zhang","doi":"10.1016/j.vesic.2022.100015","DOIUrl":"10.1016/j.vesic.2022.100015","url":null,"abstract":"<div><p>Liquid biopsy is a valuable tool in oncology with its advantages of non-invasiveness, longitudinal sampling, and capturing the intra- and inter-tumor heterogeneity. Small extracellular vesicles (sEVs) are released by cells into various biological fluids, providing a window to ascertain the cellular status of the source cells. Although many aspects of sEV biology are still enigmatic, analysis of sEV contents in biofluids offers readouts with broad applications, and may be superior or complementary to other assays of liquid biopsy. sEVs carry cell-derived biomaterials, including nucleic acids, proteins, lipids, and metabolites. RNAs are dominant components packed in sEVs, consisting of various biotypes. Protected by the phospholipid bilayer outer membrane of the sEVs, sEV RNAs are remarkably stable. Therefore, the RNA cargos originated from the cancer cells might have high potential as biomarkers in analysis of oncological features. This review will (1) characterize the RNA species loaded into sEVs as well as the related RNA metabolism; (2) summarize the molecular mechanisms of RNA sorting into sEVs, and (3) discuss the potential of using liquid biopsy of sEV RNAs in oncology for early diagnosis of tumor, assessment of tumor burden, response to therapy and monitoring minimal residual disease for recurrence and disease progression.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000105/pdfft?md5=c7e3c8140ad3c669eaf9324e681432da&pid=1-s2.0-S2773041722000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43268004","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: 3

Exosome-driven liquid biopsy for breast cancer: Recent advances in isolation, biomarker identification and detection 乳腺癌外泌体驱动液体活检:分离、生物标志物鉴定和检测的最新进展

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100006

Junjie Zhao , Lizhou Xu , Dongjie Yang , Huijing Tang , Yalin Chen , Xunzhi Zhang , Yunsheng Xu , Rongying Ou , Danyang Li

引用次数: 6

PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis PD-L1抗体外泌体疫苗通过同时原位激活T细胞和阻断PD-1/PD-L1轴来增强癌症免疫治疗

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100012

Xinyue Dai , Zhaoshuo Wang , Miao Fan , Huifang Liu , Xinjian Yang , Xueyi Wang , Xiaohan Zhou , Yunlu Dai , Jinchao Zhang , Zhenhua Li

{"title":"PD-L1 antibodies-armed exosomal vaccine for enhanced cancer immunotherapy by simultaneously in situ activating T cells and blocking PD-1/PD-L1 axis","authors":"Xinyue Dai , Zhaoshuo Wang , Miao Fan , Huifang Liu , Xinjian Yang , Xueyi Wang , Xiaohan Zhou , Yunlu Dai , Jinchao Zhang , Zhenhua Li","doi":"10.1016/j.vesic.2022.100012","DOIUrl":"10.1016/j.vesic.2022.100012","url":null,"abstract":"<div><p>Tumor immunotherapy significantly rewards antigen-specific T-cell responses, which have been recognized as the foundation of adaptive immune responses. However, due to the immunosuppressive effects of the tumor microenvironment, it is still hard to activate T cells in situ. Especially, antigen-specific T cell activity is further limited as tumor cells can evade T cell attack via PD-1/PD-L1 axis. During this work, we used a dendritic cells (DCs)-derivate exosome vaccine to build an immunotherapeutic system that can simultaneously mediate antigenic T cell activity by carrying T cells activating CD80 and MHC to induce humoral immunity. More importantly, in order to interrupt tumor immune escape, we also engineered anti-PD-L1 antibodies (aPD-L1) to block PD-1/PD-L1 axis at the same time. Our antigens-feeding DCs-exosomes with aPD-L1 engineering represents a promising strategy for enhanced cancer immunotherapy by robust activating T cells. The outcomes demonstrated that Exo-OVA-aPD-L1 was successful in inhibiting the growth, recurrence, and metastasis of melanoma.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000075/pdfft?md5=f8857c50cc77e4b859d5feff22fff131&pid=1-s2.0-S2773041722000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41261453","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: 4

Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells 硫酸乙酰肝素蛋白聚糖介导的细胞外小泡内化通过靶向肝星状细胞改善肝纤维化

Extracellular vesicle Pub Date : 2022-12-01 DOI: 10.1016/j.vesic.2022.100018

Rongrong Li , Chen Wang , Manqian Zhou , Yue Liu , Shang Chen , Zihan Chai , Haoyan Huang , Kaiyue Zhang , Zhibo Han , Guoqiang Hua , Nadia Benkirane-Jessel , Zhong-Chao Han , Zongjin Li

{"title":"Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells","authors":"Rongrong Li , Chen Wang , Manqian Zhou , Yue Liu , Shang Chen , Zihan Chai , Haoyan Huang , Kaiyue Zhang , Zhibo Han , Guoqiang Hua , Nadia Benkirane-Jessel , Zhong-Chao Han , Zongjin Li","doi":"10.1016/j.vesic.2022.100018","DOIUrl":"10.1016/j.vesic.2022.100018","url":null,"abstract":"<div><p>Accumulating evidence shows that stem cell-derived extracellular vesicles (EVs) have shown great promise for tissue regeneration and are considered an alternative to cell-based therapy. However, the mechanisms by which EVs induce tissue repair have not been well demonstrated. Previous work indicates that activation of hepatic stellate cells (HSCs) may contribute to the progression of liver fibrosis. Here, we investigate the therapeutic potential of EVs derived from human placental mesenchymal stem cells (hP-MSCs) for the treatment of carbon tetrachloride (CCl4)-induced liver injury. Our data revealed that EVs derived from hP-MSCs effectively ameliorate liver injury by attenuating inflammation and fibrosis. Further data revealed that heparan sulfate proteoglycans (HSPGs) on the surface of HSCs mediate the internalization of EVs. Furthermore, EVs could inhibit the epithelial–mesenchymal transition (EMT) process in HSCs through the downregulated TGF-<span><math><mi>β</mi></math></span>/Smad pathway, which was mediated by miR-744-5p in EVs. Meanwhile, glycosaminoglycans on the surface of EVs play a crucial anti-inflammatory role. In conclusion, our results provide evidence that hP-MSC-derived EVs promote the recovery of liver injury by targeting HSPGs on HSCs and inhibiting liver inflammation through glycosaminoglycans from EVs. These findings may provide a novel theoretical basis for the treatment of liver fibrosis based on EVs.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"1 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041722000130/pdfft?md5=d75954f4d1b9af37bd48505b0a9c2691&pid=1-s2.0-S2773041722000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46753630","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: 2