Pub Date : 2021-10-19DOI: 10.51335/ORGANOID.2021.1.E9
Y. Song, Man Ryul Lee
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.
{"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}
Pub Date : 2021-08-15DOI: 10.51335/organoid.2021.1.e14
SeonJu Park, Yong kyun Kim
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.
{"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}
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.
{"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}
Pub Date : 2021-06-19DOI: 10.51335/ORGANOID.2021.1.E10
H. Kim
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.
{"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}
Pub Date : 2021-05-30DOI: 10.51335/organoid.2021.1.e7
Ji Hye Park, Jaemeun Lee, Sun-Hyun Park, Ki-Suk Kim
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.
{"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}
Pub Date : 2021-05-30DOI: 10.51335/ORGANOID.2021.1.E8
D. Kim, S. Kim
Increasing levels of fine environmental dust particles due to industrialization and emerging respiratory illnesses, such as coronavirus disease 2019, pose serious threats to human life. The use of organoids for disease modeling and drug screening has been proposed as a new treatment approach for respiratory diseases. As discussed in this review, various pathogen models, genetic disease models, and patient-derived lung cancer organoid models have been reported for disease modeling and drug testing using human airway organoids. Despite these promising recent advances, several issues must be addressed before the disease modeling potential of human airway organoids can be fully realized. If systematic methods to produce mature airway organoids can be developed, and reproducible organoid models can be implemented using standardized protocols, airway organoids will likely become valuable respiratory disease models and drug screening tools.
{"title":"Disease modeling and drug screening using human airway organoids: a systematic review","authors":"D. Kim, S. Kim","doi":"10.51335/ORGANOID.2021.1.E8","DOIUrl":"https://doi.org/10.51335/ORGANOID.2021.1.E8","url":null,"abstract":"Increasing levels of fine environmental dust particles due to industrialization and emerging respiratory illnesses, such as coronavirus disease 2019, pose serious threats to human life. The use of organoids for disease modeling and drug screening has been proposed as a new treatment approach for respiratory diseases. As discussed in this review, various pathogen models, genetic disease models, and patient-derived lung cancer organoid models have been reported for disease modeling and drug testing using human airway organoids. Despite these promising recent advances, several issues must be addressed before the disease modeling potential of human airway organoids can be fully realized. If systematic methods to produce mature airway organoids can be developed, and reproducible organoid models can be implemented using standardized protocols, airway organoids will likely become valuable respiratory disease models and drug screening tools.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"309 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78917085","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}
Pub Date : 2021-04-10DOI: 10.51335/organoid.2021.1.e6
C. Yeo, Y. Yun, Dong Hyuck Ahn, Y. Hwang, Seung Hee Yang, Hyobin Won, Hyeong Jun Cho, Chan Kwon Park, S. Kim, Jong Y. Park
Lung cancer, which remains a major cause of mortality worldwide, is a histologically diverse condition and demonstrates substantial phenotypic and genomic diversity among individual patients, manifesting as both intertumoral and intratumoral heterogeneity. This heterogeneity has made it difficult to develop lung cancer models. Two-dimensional (2D) cancer cell lines have been used to study genetic and molecular alterations in lung cancer. However, cancer cell lines have several disadvantages, including random genetic drift caused by long-term culture, a lack of annotated clinical data, and most importantly, the fact that only a subset of tumors shows 2D growth on plastic. Three-dimensional models of cancer have the potential to improve cancer research and drug development because they are more representative of cancer biology and its diverse pathophysiology. Herein, we present an integrated review of current information on preclinical lung cancer models and their limitations, including cancer cell line models, patient-derived xenografts, and lung cancer organoids, and discuss their possible therapeutic applications for drug discovery and screening to guide precision medicine in lung cancer research. Altogether, the success rate of generating lung cancer organoids must be improved, and a lung cancer organoid culture system is necessary to achieve the goal of designing an individualized therapeutic strategy for each lung cancer patient.
{"title":"Therapeutic applications of three-dimensional organoid models in lung cancer","authors":"C. Yeo, Y. Yun, Dong Hyuck Ahn, Y. Hwang, Seung Hee Yang, Hyobin Won, Hyeong Jun Cho, Chan Kwon Park, S. Kim, Jong Y. Park","doi":"10.51335/organoid.2021.1.e6","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e6","url":null,"abstract":"Lung cancer, which remains a major cause of mortality worldwide, is a histologically diverse condition and demonstrates substantial phenotypic and genomic diversity among individual patients, manifesting as both intertumoral and intratumoral heterogeneity. This heterogeneity has made it difficult to develop lung cancer models. Two-dimensional (2D) cancer cell lines have been used to study genetic and molecular alterations in lung cancer. However, cancer cell lines have several disadvantages, including random genetic drift caused by long-term culture, a lack of annotated clinical data, and most importantly, the fact that only a subset of tumors shows 2D growth on plastic. Three-dimensional models of cancer have the potential to improve cancer research and drug development because they are more representative of cancer biology and its diverse pathophysiology. Herein, we present an integrated review of current information on preclinical lung cancer models and their limitations, including cancer cell line models, patient-derived xenografts, and lung cancer organoids, and discuss their possible therapeutic applications for drug discovery and screening to guide precision medicine in lung cancer research. Altogether, the success rate of generating lung cancer organoids must be improved, and a lung cancer organoid culture system is necessary to achieve the goal of designing an individualized therapeutic strategy for each lung cancer patient.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87055180","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}
Pub Date : 2021-01-20DOI: 10.51335/organoid.2021.1.e1
Hyung-Ryong Kim
{"title":"Presidential message","authors":"Hyung-Ryong Kim","doi":"10.51335/organoid.2021.1.e1","DOIUrl":"https://doi.org/10.51335/organoid.2021.1.e1","url":null,"abstract":"","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80539779","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}
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