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Fundamental signaling pathways for glioblastoma drug resistance and developing robust organoid models for drug discovery 胶质母细胞瘤耐药的基本信号通路和开发药物发现的强大类器官模型
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-03-25 DOI: 10.51335/organoid.2022.2.e8
Athira Pratap, Eun‐Jung Lim, I. Kwak, Byoung-San Moon
{"title":"Fundamental signaling pathways for glioblastoma drug resistance and developing robust organoid models for drug discovery","authors":"Athira Pratap, Eun‐Jung Lim, I. Kwak, Byoung-San Moon","doi":"10.51335/organoid.2022.2.e8","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e8","url":null,"abstract":"This article presents a review of the current literature on the molecular mechanisms of treatment resistance in glioblastoma. As mounting research continues to explore novel methods of treating glioblastoma, from using organoid models for drug screening to developing novel cellular therapies, it is critical to understand the fundamental molecular landscape that makes glioblastoma difficult to treat. This review explores the means of chemoresistance to the conventional chemotherapy temozolomide. Consideration of DNA repair pathways, p53-mediated apoptosis and autophagy, convergent proliferation pathways, and epigenetic mechanisms demonstrate avenues for the development of sophisticated drug targets and combination treatments. Ultimately, this article highlights each of these mechanisms and presents referential material for future endeavors in organoid-based drug screening.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76592512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging organoid-based platforms to study salivary gland hypofunction 新兴的基于器官的平台研究唾液腺功能减退
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-03-24 DOI: 10.51335/organoid.2022.2.e2
Yoojin Seo, Hyung-Sik Kim
{"title":"Emerging organoid-based platforms to study salivary gland hypofunction","authors":"Yoojin Seo, Hyung-Sik Kim","doi":"10.51335/organoid.2022.2.e2","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e2","url":null,"abstract":"Xerostomia is a pathologic condition of hyposalivation due to salivary gland (SG) dysfunction. Although xerostomia significantly affects the quality of patients’ life, there is no satisfactory treatment for this disease. Importantly, the senior population is more susceptible to xerostomia than younger individuals and the prevalence of the disease is much higher in elderly women than in men. However, the mechanisms underlying these clinical correlations have not yet been elucidated and further studies are required. Given that cell lines exhibiting saliva-producing abilities are not available, the generation and maturation of salivary gland organoids (SGOs) have been spotlighted as a modeling system to investigate the homeostasis of SG stem cells, as well as the pathophysiology of SGs in disease. In this review article, we will review the latest reports dealing with the generation and maturation of SGOs by defining the stem cells in SGs. We will also discuss the recent literature proposing strategies to model disease and regenerate damaged tissues.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79360534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glioblastoma organoid technology: an emerging preclinical models for drug discovery 胶质母细胞瘤类器官技术:药物发现的新兴临床前模型
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-02-25 DOI: 10.51335/organoid.2022.2.e7
D. C. Batara, Shuchang Zhou, Moon-Chang Choi, Sung-Hak Kim
{"title":"Glioblastoma organoid technology: an emerging preclinical models for drug discovery","authors":"D. C. Batara, Shuchang Zhou, Moon-Chang Choi, Sung-Hak Kim","doi":"10.51335/organoid.2022.2.e7","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e7","url":null,"abstract":"Glioblastoma multiforme (GBM) is the most prevalent type of primary brain tumor among adults, and it has a median overall survival of 12 to 15 months upon diagnosis. Despite significant improvements in GBM research, therapeutic options are still limited and survival rates have not significantly improved. Accordingly, clinical and translational studies are hampered due to the lack of suitable preclinical models that accurately reflect the brain tumor architecture and its microenvironment. Scientists have recently developed cerebral organoids, which are artificial 3-dimensional brain-like tissue. Organoid technology provides new cancer modeling options, which could help us better understand GBM pathogenesis and design personalized treatments. In this review, we summarize recent developments in organoid GBM models, highlighting their advantages in cancer modeling, as well as their challenges and limitations and potential future directions in GBM therapy.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78675024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Biomimetic in vitro heart platforms for drug development 用于药物开发的体外仿生心脏平台
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-02-16 DOI: 10.51335/organoid.2022.2.e1
Sungwoo Cho, S. Ko
{"title":"Biomimetic in vitro heart platforms for drug development","authors":"Sungwoo Cho, S. Ko","doi":"10.51335/organoid.2022.2.e1","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e1","url":null,"abstract":"New drug development is currently very expensive and time-consuming. In addition, some drugs that are approved after animal and clinical trials have their approval revoked because of adverse effects. About 30% of such drugs have heart side effects. Conventional cell-based drug toxicity tests are performed under conditions entirely different from the in vivo environment, and animal testing for drug evaluation has limitations because of differences between species. Therefore, researchers are increasingly focusing on developing models that can overcome these limitations to enable accurate drug toxicity tests. This review outlines biomimetic in vitro heart platforms, such as heart organoids, 3-dimensional bioprinting, and heart-on-a-chip devices, and describes their advantages, limitations, future perspectives. The development and use of effective cardiac biomimetic models could contribute to the development of alternatives to animal testing by providing more specific information on drug metabolism and reducing the rate of failure in later stages of drug development.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81774248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances in liver organoids and their use in in vitro modeling of non-alcoholic fatty liver disease 肝类器官的研究进展及其在非酒精性脂肪性肝病体外模型中的应用
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-01-25 DOI: 10.51335/organoid.2022.2.e6
Kyun Yoo Chi, Jong-Hoon Kim
{"title":"Recent advances in liver organoids and their use in in vitro modeling of non-alcoholic fatty liver disease","authors":"Kyun Yoo Chi, Jong-Hoon Kim","doi":"10.51335/organoid.2022.2.e6","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e6","url":null,"abstract":"The liver is involved in physiological activities critical for survival. Chronic liver disease (CLD) frequently progresses to life-threatening liver failure, as evidenced by CLD patients’ high morbidity and mortality rates. Over the years, non-alcoholic fatty liver disease (NAFLD) has received significant attention as an etiology of CLD given its increasing prevalence and progression towards severe pathological conditions such as fibrosis. To answer the urgent need for effective therapeutics that treat CLD, an advanced cellular model, the liver organoid, is used to model and study the complex pathophysiology of NAFLD. Liver organoids recapitulate in vivo aspects of liver tissue such as 3-dimensional cell-cell and cell-extracellular matrix interactions and biomolecular gradients. Moreover, liver organoids can be readily generated from patient-specific liver tissues and induced pluripotent stem cells, enabling their use in a wide range of personalized clinical applications. In recent research, numerous attempts have been made to establish multicellular liver organoids capable of modeling disease phenotypes that involve parenchymal and non-parenchymal liver cells. In this review, we focus on recent advances in liver organoids and highlight the applicability of organoids for modeling NAFLD within the context of cellular sources and composition.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82565643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The application of intestinal organoids and their co-culture systems in the study of gastrointestinal diseases 肠道类器官及其共培养系统在胃肠道疾病研究中的应用
Brain Organoid and Systems Neuroscience Journal Pub Date : 2022-01-15 DOI: 10.51335/organoid.2022.2.e3
Panida Sittipo, Y. Lee
{"title":"The application of intestinal organoids and their co-culture systems in the study of gastrointestinal diseases","authors":"Panida Sittipo, Y. Lee","doi":"10.51335/organoid.2022.2.e3","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e3","url":null,"abstract":"The 3-dimensional culture of intestinal organoids provides insights into the phenotype and physiology of the intestine. Intestinal organoids comprise intestinal stem cells and differentiated intestinal epithelial cells; they can be stably cultured over the long term and can be genetically manipulated. Current strategies for intestinal organoid co-culture with other cells existing in the intestinal tract and gut microbiota have been established to mimic the intestinal microenvironment and study host-microbial interactions. Therefore, intestinal organoids are promising tools for basic and translational research in gastroenterology. Gastrointestinal diseases are disorders of the intestinal tract that result in a reduced quality of life, and a deep understanding of these diseases would be effective for their treatment. In this review, we discuss how intestinal organoids and intestinal organoids integrated with cellular and microbiota niche components are biologically and physiologically relevant tools for the investigation of gastrointestinal diseases.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"143 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80318461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
A novel method for the isolation of CD45-positive and CD45-negative cells from malignant pleural effusion 一种分离恶性胸腔积液cd45阳性和cd45阴性细胞的新方法
Brain Organoid and Systems Neuroscience Journal Pub Date : 2021-12-15 DOI: 10.51335/organoid.2021.1.e13
Jimin Choi, Jeong Uk Lim, Wooil Kim, Dong Woo Lee, S. Kwon, Sang-Hyun Lee
{"title":"A novel method for the isolation of CD45-positive and CD45-negative cells from malignant pleural effusion","authors":"Jimin Choi, Jeong Uk Lim, Wooil Kim, Dong Woo Lee, S. Kwon, Sang-Hyun Lee","doi":"10.51335/organoid.2021.1.e13","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e13","url":null,"abstract":"Background: Patient-derived malignant pleural effusion (MPE) samples can be used to identify a patient-specific drug combination since MPE samples are readily available and cost-effective tumor cell sources. However, the isolation of target cancer cells from MPE has been inefficient because MPE samples contain a complex mixture of immune cells, non-cancerous cells, and cancer cells. Hence, new methods need to be developed to effectively isolate target cancer cells from MPE samples that can be used for 3-dimensional (3D) cell culture. Patient-derived in vitro 3D tumor models are expected to facilitate more precise drug treatment.Methods: MPE samples were obtained from Seoul St. Mary’s Hospital, The Catholic University of Korea with consent from patients previously diagnosed with lung adenocarcinoma. We isolated target cells from MPE samples using 2 different Percoll-gradient centrifugation methods.Results: The use of 40% and 75% Percoll-gradient centrifugation led to a clearer separation of CD45-positive (CD45pos) and CD45-negative (CD45neg) cells than the traditional 44% and 67% Percoll-gradient centrifugation method.Conclusion: Our findings strongly suggest that the 40% and 75% Percoll-gradient centrifugation method is more useful for the isolation of CD45pos or CD45neg cells than the previously described Percoll-gradient centrifugation method. Furthermore, our novel method was useful for the isolation of MPE-derived target cancer cells that can be used to construct in vitro patient-specific 3D tumor models.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85946479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bronchioalveolar organoids as a tool to study transforming growth factor-β and cigarette smoke–induced lung pathology 细支气管肺泡类器官作为研究转化生长因子-β和香烟引起的肺部病理的工具
Brain Organoid and Systems Neuroscience Journal Pub Date : 2021-11-15 DOI: 10.51335/organoid.2021.1.e12
S. Jeong, Jung-Hyun Kim, Roya Rasaei, Seok-Ho Hong
{"title":"Bronchioalveolar organoids as a tool to study transforming growth factor-β and cigarette smoke–induced lung pathology","authors":"S. Jeong, Jung-Hyun Kim, Roya Rasaei, Seok-Ho Hong","doi":"10.51335/organoid.2021.1.e12","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e12","url":null,"abstract":"Respiratory medicine has high barriers to new drug development, with fewer approved new treatments and candidate drugs and a higher failure rate than other common disease fields. Most of the major candidate drugs identified in preclinical animal studies fail in the clinical setting because of differences between animal models and humans. Therefore, the rapid development of 3-dimensional (3D) organoid-based disease models that recapitulate human pathological development has attracted increasing attention in drug development and personalized medicine. In the present study, we generated bronchoalveolar organoids (BAOs) from human pluripotent stem cells (hPSCs) and assessed their potential as a pulmonary disease model. Derived BAOs contained the expected spectrum of differentiated cells, including alveolar progenitors, type 1 and 2 alveolar epithelial cells, basal cells, secretory cells, ciliated cells, and mesenchymal cells. When the BAOs were exposed to transforming growth factor-beta, both fibrosis- and inflammation-related transcripts were significantly upregulated compared to the control. In addition, the exposure of BAOs to cigarette smoking extract induced increased levels of nitric oxide in a dose-dependent manner, as well as upregulating oxidative stress-related and pro-inflammatory genes. These findings suggest that hPSC-derived BAOs could be a promising platform for modeling pulmonary fibrosis and chronic obstructive pulmonary disease and testing drug efficacy.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82886737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell transcriptomics of lung organoids 肺类器官的单细胞转录组学
Brain Organoid and Systems Neuroscience Journal Pub Date : 2021-10-19 DOI: 10.51335/ORGANOID.2021.1.E9
Y. Song, Man Ryul Lee
{"title":"Single-cell transcriptomics of lung organoids","authors":"Y. Song, Man Ryul Lee","doi":"10.51335/ORGANOID.2021.1.E9","DOIUrl":"https://doi.org/10.51335/ORGANOID.2021.1.E9","url":null,"abstract":"The in vitro application of human pluripotent stem cell- or adult stem cell-derived lung organoids has the potential to revolutionize lung disease research, but there are several limitations in the consistent implementation of lung organoids resulting from the structural diversity of the lung tissues and the variety of cell types (more than 40 resident cell types) populating these tissues. However, the evaluation of these complexities using a combination of lung organoids and single-cell transcriptomics has made it possible to identify several key cell types and sub-populations critical to the development of robust in vitro organoid models. Recent studies have started to use stem cells to produce these organoids, making it possible to mimic complex 3-dimensional tissues. Furthermore, single-cell mRNA sequencing allows critical comparisons of the transcriptome, which may help focus future research in the field of lung disease.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"155 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88206641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Strategies for vascularization in kidney organoids 肾类器官血管化策略
Brain Organoid and Systems Neuroscience Journal Pub Date : 2021-08-15 DOI: 10.51335/organoid.2021.1.e14
SeonJu Park, Yong kyun Kim
{"title":"Strategies for vascularization in kidney organoids","authors":"SeonJu Park, Yong kyun Kim","doi":"10.51335/organoid.2021.1.e14","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e14","url":null,"abstract":"The establishment of protocols for differentiating kidney organoids from human pluripotent stem cells (hPSCs) has potential for the application of kidney organoids in regenerative medicine. However, the primary obstacle to the regenerative application of hPSC-derived kidney organoids is precise vascularization due to the lack of vasculature in hPSC-derived kidney organoids. In this article, we review the recent methodologies for developing vasculature of kidney organoids to overcome this limitation of kidney organoids, together with a discussion of their clinical applications.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79720570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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