{"title":"Disease modeling in organoid cultures: a new tool for studying viruses","authors":"Jaewon Cho, Eun-Hye Hong, Hyun-Jeong Ko","doi":"10.51335/organoid.2022.2.e15","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e15","url":null,"abstract":"In vitro experiments have been widely used for more than a century to elucidate molecular mechanisms in cells and pathogen-host interactions, as well as for drug screening. Cell lines have been modified to reflect researchers’ specific purposes, and in vitro experiments have become fundamental for biological studies, with an ability to replace in vivo experiments. However, immortalized cell lines and cancer-derived cell lines have the limitation of losing their inherent properties, potentially resulting in changes in signaling pathways and cell metabolism. These limitations have made it necessary for researchers to find a novel way to overcome the limitations of cell lines. In recent years, organoids, which are 3-dimensional multicellular in vitro tissue constructs that fundamentally imitate in vivo organs, have been developed as alternative systems to study various aspects of organs. Herein, we review recent studies on the application of organoids in disease modeling, with a focus on intestine, lung, and tonsil organoids. These 3 organoids have been of utmost interest to researchers since their initial development. Most importantly, organoids are novel experimental models that can simulate in vivo organs and can therefore replace or support existing in vitro and in vivo models.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75351411","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":"Understanding the cellular pathogenesis of COVID-19 symptoms using organoid technology","authors":"Y. Che, Yong Jun Kim","doi":"10.51335/organoid.2022.2.e16","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e16","url":null,"abstract":"Patients with coronavirus disease 2019 (COVID-19), which has recently caused a pandemic, have reported symptoms of coronavirus infection that are not well understood by the medical community in general. After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several symptoms, including acute clinical signs and possible sequelae, manifest in multiple organs. It is necessary to precisely identify the cells susceptible to SARS-CoV-2 infection in order to comprehend the mechanism of symptom occurrence, identify molecular targets for therapeutic development, and prevent current or future threats. Following the use of cell lines, animal models, and stem cell-derived symptom-relevant cells, recent research on the pathophysiology of human diseases has utilized organoid models. This article provides a summary of recent research on the tissue- or organ-specific cellular targets of SARS-CoV-2 aiming to understand the pathophysiology of COVID-19.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88151737","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":"Applications of human brain organoids","authors":"A. Muotri","doi":"10.51335/organoid.2022.2.e13","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e13","url":null,"abstract":"The human brain is formed inside the womb. Current imaging technologies are not sensitive enough to investigate how human brains are formed at the molecular and cellular levels. By recreating neurodevelopment in the lab, we have a unique opportunity to learn how the human brain develops from the embryo. The brain organoid technology was initially developed by Dr. Yoshiki Sasai in 2008 [1]. His pioneer publication revealed that it was possible to push neural differentiation of human pluripotent stem cells in suspension and let the cells self-aggregate, after which they form a tissue that resembles the human fetal cortex. Several other labs have developed other improved ways to create brain organoids, making them more robust and more reliable [2]. Brain organoids are not fully vascularized, not all cell types are represented, and there are no optimized culture conditions to grow human brain organoids [3].","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89558161","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}
Hanbyeol Lee, Jeong Suk Im, Daejin Choi, Jieun An, Subin Kim, Seunghee Yeon, Seulgi Yoon, Dong-Hun Woo
{"title":"Three-dimensional cardiac organoid formation accelerates the functional maturation of human induced pluripotent stem cell-derived cardiomyocytes","authors":"Hanbyeol Lee, Jeong Suk Im, Daejin Choi, Jieun An, Subin Kim, Seunghee Yeon, Seulgi Yoon, Dong-Hun Woo","doi":"10.51335/organoid.2022.2.e14","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e14","url":null,"abstract":"Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) offer a promising source for heart regeneration, disease modeling, and drug screening. Recent developments in organoid technology have made it possible to study how hiPSC-derived CMs interact together, and this culture system mimics the tissue environment and behavior of the cardiac cells in our body. However, the similarities and differences between conventional 2-dimensional (2D) culture and 3-dimensional (3D) organoid culture systems for CM differentiation have been incompletely elucidated. To study how the individual microenvironment formed by each culture system affects the properties of CMs differentiated from hiPSCs, we conducted a comparative study between 2D monolayer and direct 3D cardiac organoid (hiCO) differentiation from hiPSCs throughout the sequential differentiation stages. Although identical differentiation cues were applied to hiPSCs, the 3D differentiation system strongly exhibited higher mesoderm commitment and cardiac induction than 2D monolayer differentiation. In the late stage of differentiation, the 3D hiCOs showed a higher frequency of a mature myofibrillar isoform switching in sarcomere structure of differentiated CMs than was observed in monolayer culture, although over 94% of cardiac troponin T-positive cells resulted at the end point of differentiation in both systems. Furthermore, the accelerated structural maturation in 3D hiCOs resulted in increased expression of cardiac-specific ion channel genes and Ca2+ transient properties, with a high signal amplitude and rapid contractility. The present study provides details surrounding the 2D and 3D culture methods for CM differentiation from iPSCs, and focuses on 3D cell culture as an improved strategy for approaching and applying cardiac maturation.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79147077","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}
Min Jung Kim, Jaeseo Lee, Seon Ju Mun, M. Son, Jung-Hyun Kim
{"title":"Standard operating protocol of hepatic organoid differentiation from human induced pluripotent stem cells","authors":"Min Jung Kim, Jaeseo Lee, Seon Ju Mun, M. Son, Jung-Hyun Kim","doi":"10.51335/organoid.2022.2.e5","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e5","url":null,"abstract":"Mature liver organoids are promising cell sources for research to understand the pathology underlying a variety of conditions affecting the liver, including end-stage chronic liver disease. Although several methods exist for the differentiation of mature hepatic organoids derived from human induced pluripotent stem cells (hiPSCs), organoid generation can fail due to various experimental culture conditions. Therefore, we established a standard operating protocol for generating mature and expandable hepatic organoids derived from hiPSCs, and we made the starting materials available to facilitate the wide use of the protocol.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75122657","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":"Progress, prospects, and limitations of organoid technology","authors":"Jin Hee Park, Do Gyeung Byeun, Jung Kyu Choi","doi":"10.51335/organoid.2022.2.e9","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e9","url":null,"abstract":"Organoids are mini-organs generated through in vitro 3-dimensional culture that mimic some of the structural and physiological functions of real organs. In recent research, various organoids have been derived from pluripotent stem cells or multipotent organ-specific adult stem cells in vitro and have been used in regenerative medicine, disease modeling, precision medicine, toxicology studies, and drug discovery. However, research on reproduction-related organoids has not been comprehensive, and some limitations need to be addressed for culturing these organoids. In this review, we discuss the historical advances, major recent developments, limitations, and potential of organoid culture, including human reproductive organoids.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76055395","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 and challenges in organoid-on-a-chip technology","authors":"Intan Rosalina Suhito, Tae-Hyung Kim","doi":"10.51335/organoid.2022.2.e4","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e4","url":null,"abstract":"Conventional 2-dimensional cell culture poorly mimics human-relevant models, which is considered a major challenge in biological research. Organoids are a recent breakthrough in 3-dimensional (3D) in vitro tissue engineering that better reflect the physiological, morphological, and functional properties of in vivo organs (e.g., brain, heart, kidney, lung, and liver). Consequently, organoids are extensively used in various impactful biomedical applications including organ development, disease modeling, and clinical drug testing. However, organoid technology still has several limitations, including low reproducibility, vascularization, limited nutrient uptake and distribution (affecting the level of organoid maturation), lack of standardization, and intra-clonal variability. Efforts have been made to overcome these shortcomings of organoid culture. Microfluidic technology has successfully facilitated the establishment of organoid-on-a-chip systems, which effectively improve the structural and physiological features of organoids in a controlled manner. This review discusses the recent advances and developments in organoid-on-a-chip technology. We hope that this study will motivate researchers to explore the possible engagement between microfluidic devices and self-assembled 3D cell cultures to leverage the enhanced quality of organoids, which will have favorable impacts on future tissue regeneration and regenerative therapies.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76090375","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}
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}
{"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}
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}