{"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}
{"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}
{"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}
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}
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}
{"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}
{"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}
{"title":"Trends in the global organoid technology and industry: from organogenesis in a dish to the commercialization of organoids","authors":"Hanbyeol Lee, Jeong Suk Im, Daejin Choi, Dong-Hun Woo","doi":"10.51335/organoid.2021.1.e11","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e11","url":null,"abstract":"Animal models have been standard methods for non-clinical research in drug development for decades. However, many drugs that have shown satisfactory results in non-clinical studies have failed in the clinical stage, presumably because animal data are not fully convertible to human data. Human organoid technology has recently been considered as an alternative to existing non-clinical testing methods, and it could potentially serve a role as a bridge from non-clinical to clinical trials, compensating for the current limitations arising from non-clinical animal models. For this reason, organoid technology is being utilized in various fields of research including academic studies, disease modeling, drug screening, biobanks, and regenerative medicine. In addition, as organoid technology progressively develops, it has been combined with bioengineering to develop applications from manufacturing to drug evaluation platforms, which is leading to a demand for commercialization of organoids for researchers. In accordance with this global trend, the organoid industry continues to grow throughout the world, and organoid research and the market for organoids have been boosted by the demand for efficient and rapid drug development in response to the coronavirus disease 2019 pandemic. In this review, we discuss recent global trends in organoid research, based on tissue types and applications, as well as the organoid market and its prospects.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82224679","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}
{"title":"Engineered models for studying blood-brain-barrier-associated brain physiology and pathology","authors":"H. Kim","doi":"10.51335/ORGANOID.2021.1.E10","DOIUrl":"https://doi.org/10.51335/ORGANOID.2021.1.E10","url":null,"abstract":"The blood-brain barrier (BBB) is a transport barrier that suppresses the translocation of potentially harmful substances to the brain tissue. Although the BBB is known to be associated with many kinds of neuropathology, such as neuroinflammation and neurodegenerative diseases, the conventionally used animal and Transwell models cannot provide sufficient information due to genetic and functional heterogeneity in comparison with humans and limited monitoring capabilities. Recently, human cell-based three-dimensional BBB models have been developed, and these models provide in vivo-like BBB structures and functions. In this review, we provide an overview of the recent advances in BBB models with a particular focus on the simulation of BBB-associated brain physiology and neuropathology. To this end, important factors for recapitulating the in vivo characteristics of the BBB are described. Furthermore, approaches to recapitulate the BBB physiology using engineering methods are summarized. The applications of BBB models in the study of neuropathology, such as inflammation and neurodegenerative diseases, are also presented.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85889191","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}
Ji Hye Park, Jaemeun Lee, Sun-Hyun Park, Ki-Suk Kim
{"title":"Optimizing a three-dimensional spheroid clearing method for the imaging-based evaluation of cardiotoxicity","authors":"Ji Hye Park, Jaemeun Lee, Sun-Hyun Park, Ki-Suk Kim","doi":"10.51335/organoid.2021.1.e7","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e7","url":null,"abstract":"Toxicity evaluation based on two-dimensional cell culture shows differences from clinical results and has the disadvantage of not accurately reflecting cell-to-cell cross-signaling. Since almost all cells in the human body are arranged in a three-dimensional structure and constitute a tissue, the in vitro reproduction of three-dimensional tissues composed of human cells can be used as effective models for drug development and toxicity evaluation. The clearing technique improves image resolution and can be used to generate three-dimensional bio-images throughout the organized structure, improving the efficiency of toxicity evaluation for disease models using spheroids. Herein, we report the first optical spheroid clearing protocol for an image-based toxicity prediction model. In our results, spheroid clearing significantly increased fluorescence intensity and enabled image-based toxicity prediction. We propose that this spheroid clearing method can be utilized for image-based cardiotoxicity evaluation. Furthermore, we also present the possibility that our protocol can be utilized for patient-tailored toxicity prediction.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81953895","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}