Pub Date : 2022-08-25DOI: 10.51335/organoid.2022.2.e22
Tae Il Kim
Since the first successful establishment of organoids from adult intestinal stem cells, organoid technology has rapidly developed. With advances in normal organoid technology, intestinal disorders, such as colorectal tumors and inflammatory bowel disease, have been major target diseases for patient-derived organoid (PDO) development. PDO biobanking for colorectal cancer has subsequently been developed, and some reports have shown the possibility of using PDO models to predict anticancer drug responses. However, to apply these models to real-world practice, we need more long-term clinical follow-up data from further large-scale PDO biobanks, as well as advanced technology for more rapid and efficient PDO establishment. In addition, in the field of regenerative medicine, the implantation of healthy intestinal PDOs to refractory tissue defects could be a new treatment strategy to accelerate the healing and repair of mucosal defects. This PDO technology could also be applied to inflammatory bowel diseases and serve as a very useful model for drug development via high-throughput screening of useful candidate drugs.
{"title":"Clinical applications and optimization of patient-derived organoids in intestinal diseases","authors":"Tae Il Kim","doi":"10.51335/organoid.2022.2.e22","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e22","url":null,"abstract":"Since the first successful establishment of organoids from adult intestinal stem cells, organoid technology has rapidly developed. With advances in normal organoid technology, intestinal disorders, such as colorectal tumors and inflammatory bowel disease, have been major target diseases for patient-derived organoid (PDO) development. PDO biobanking for colorectal cancer has subsequently been developed, and some reports have shown the possibility of using PDO models to predict anticancer drug responses. However, to apply these models to real-world practice, we need more long-term clinical follow-up data from further large-scale PDO biobanks, as well as advanced technology for more rapid and efficient PDO establishment. In addition, in the field of regenerative medicine, the implantation of healthy intestinal PDOs to refractory tissue defects could be a new treatment strategy to accelerate the healing and repair of mucosal defects. This PDO technology could also be applied to inflammatory bowel diseases and serve as a very useful model for drug development via high-throughput screening of useful candidate drugs.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88392256","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 : 2022-08-25DOI: 10.51335/organoid.2022.2.e25
M. Choe, M. Lee
Background: Breast cancer is a common cause of brain metastasis. Although breast cancer has relatively high survival rates, its survival rate after metastasis to the brain is lower. Conventional two-dimensional cell culture models and animal models are widely used in metastatic cancer research, and these models have tremendously contributed to the understanding of this disease. However, these models have some limitations, such as different physiological features and genetic backgrounds.Methods: We established a simple metastatic breast cancer model using human pluripotent stem cell-derived cerebral organoids (COs)—in this case, breast cancer cerebral organoids (BC-COs).Results: Using the BC-CO model, we induced the metastasis of MDA-MB-231 cells into COs by co-culture of cells with COs and compared the differences between adapted cancer cells in BC-COs and non-adapted cells. Our results showed that the proliferative capacity increased in adapted cells. Additionally, the expression levels of endothelial-mesenchymal transition markers and cancer stem cells were significantly higher in adapted cancer cells.Conclusion: We conclude that metastasis promotes the metastatic capacity of breast cancer cells. Our results also showed that the BC-CO model could be a novel tool for research on brain metastasis in breast cancer.
{"title":"A brain metastasis model for breast cancer using human embryonic stem cell-derived cerebral organoids","authors":"M. Choe, M. Lee","doi":"10.51335/organoid.2022.2.e25","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e25","url":null,"abstract":"Background: Breast cancer is a common cause of brain metastasis. Although breast cancer has relatively high survival rates, its survival rate after metastasis to the brain is lower. Conventional two-dimensional cell culture models and animal models are widely used in metastatic cancer research, and these models have tremendously contributed to the understanding of this disease. However, these models have some limitations, such as different physiological features and genetic backgrounds.Methods: We established a simple metastatic breast cancer model using human pluripotent stem cell-derived cerebral organoids (COs)—in this case, breast cancer cerebral organoids (BC-COs).Results: Using the BC-CO model, we induced the metastasis of MDA-MB-231 cells into COs by co-culture of cells with COs and compared the differences between adapted cancer cells in BC-COs and non-adapted cells. Our results showed that the proliferative capacity increased in adapted cells. Additionally, the expression levels of endothelial-mesenchymal transition markers and cancer stem cells were significantly higher in adapted cancer cells.Conclusion: We conclude that metastasis promotes the metastatic capacity of breast cancer cells. Our results also showed that the BC-CO model could be a novel tool for research on brain metastasis in breast cancer.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78723764","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 : 2022-08-18DOI: 10.51335/organoid.2022.2.e18
Suwon Kang, Eun Kyung Bong, Hyo-Min Kim, Tae-Young Roh
Cell culture systems have been widely used to address fundamental questions in biology without sacrificing animals. Three-dimensional (3D) organoids provide more information on in vivo conditions than traditional culture systems because multiple cell types in organoids interact with each other in 3D structures. Despite extensive research and advances in the organoid field, some important limitations remain and need further consideration. In this review, we summarize how organoids are generated from pluripotent stem cells and describe the recent technical progress that has made organoids more similar to in vivo tissues for the application of organoids to modeling cancer. Lastly, we briefly discuss some limitations that have been raised in this field.
{"title":"Technical advances in pluripotent stem cell-derived and tumorigenic organoids","authors":"Suwon Kang, Eun Kyung Bong, Hyo-Min Kim, Tae-Young Roh","doi":"10.51335/organoid.2022.2.e18","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e18","url":null,"abstract":"Cell culture systems have been widely used to address fundamental questions in biology without sacrificing animals. Three-dimensional (3D) organoids provide more information on in vivo conditions than traditional culture systems because multiple cell types in organoids interact with each other in 3D structures. Despite extensive research and advances in the organoid field, some important limitations remain and need further consideration. In this review, we summarize how organoids are generated from pluripotent stem cells and describe the recent technical progress that has made organoids more similar to in vivo tissues for the application of organoids to modeling cancer. Lastly, we briefly discuss some limitations that have been raised in this field.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82939031","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 : 2022-07-25DOI: 10.51335/organoid.2022.2.e17
Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, M. Son
Drug safety issues continue to occur even with drugs that are approved after the completion of clinical studies. Drug-induced liver injury (DILI) is a major obstacle to drug development, because the liver is the primary site of drug metabolism, and injuries caused during this process are severe. Conventional in vitro human liver models, such as 2-dimensional hepatic cell lines, lack in vivo physiological relevance, and animal studies have limitations in the form of species differences and regulatory restrictions. To resolve this issue, an increasing number of 3-dimensional human liver systems, including organoids, are being developed. In this review, we provide an overview of recent assessments of DILI prediction, approaches for in vitro hepatotoxicity evaluation, and a variety of advanced human liver models. We discuss the advantages, limitations, and future perspectives of current human liver models for accurate drug safety evaluations.
{"title":"Advanced human liver models for the assessment of drug-induced liver injury","authors":"Seon Ju Mun, Jaeseo Lee, Yong-Moon Shin, M. Son","doi":"10.51335/organoid.2022.2.e17","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e17","url":null,"abstract":"Drug safety issues continue to occur even with drugs that are approved after the completion of clinical studies. Drug-induced liver injury (DILI) is a major obstacle to drug development, because the liver is the primary site of drug metabolism, and injuries caused during this process are severe. Conventional in vitro human liver models, such as 2-dimensional hepatic cell lines, lack in vivo physiological relevance, and animal studies have limitations in the form of species differences and regulatory restrictions. To resolve this issue, an increasing number of 3-dimensional human liver systems, including organoids, are being developed. In this review, we provide an overview of recent assessments of DILI prediction, approaches for in vitro hepatotoxicity evaluation, and a variety of advanced human liver models. We discuss the advantages, limitations, and future perspectives of current human liver models for accurate drug safety evaluations.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91425349","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 : 2022-07-25DOI: 10.51335/organoid.2022.2.e19
Y. R. Ko, Ji min Kim, Younsoo Kang, Minsuh Kim, S. Jang
Cancer model systems that maintain the genetic and phenotypic characteristics of human cancers are crucial for the study of precision cancer medicine. In this respect, patient-derived cancer organoids have been developed as preclinical models of various human cancers, with significant advantages over previous cancer models including patient-derived xenografts and cell lines. We recently reported a culture system of patient-derived lung cancer organoids (LCOs) that retain the characteristics of patients’ tumors. Here, we describe a detailed protocol for establishing LCOs from surgically resected tumor tissues and endoscopic biopsy samples. This method improves the efficiency of setting up LCOs composed of pure cancer cells and describes an additional procedure for reconstructing LCOs after cryopreservation. We confirmed that stored LCOs had the ability to self-organize and retain the morphological and genetic characteristics of their parental tissues. They also maintained their responsive properties to certain anticancer drugs after thawing. In conclusion, our method efficiently generates LCOs that enable anticancer drug screening at the individual patient level.
{"title":"A method for culturing patient-derived lung cancer organoids from surgically resected tissues and biopsy samples","authors":"Y. R. Ko, Ji min Kim, Younsoo Kang, Minsuh Kim, S. Jang","doi":"10.51335/organoid.2022.2.e19","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e19","url":null,"abstract":"Cancer model systems that maintain the genetic and phenotypic characteristics of human cancers are crucial for the study of precision cancer medicine. In this respect, patient-derived cancer organoids have been developed as preclinical models of various human cancers, with significant advantages over previous cancer models including patient-derived xenografts and cell lines. We recently reported a culture system of patient-derived lung cancer organoids (LCOs) that retain the characteristics of patients’ tumors. Here, we describe a detailed protocol for establishing LCOs from surgically resected tumor tissues and endoscopic biopsy samples. This method improves the efficiency of setting up LCOs composed of pure cancer cells and describes an additional procedure for reconstructing LCOs after cryopreservation. We confirmed that stored LCOs had the ability to self-organize and retain the morphological and genetic characteristics of their parental tissues. They also maintained their responsive properties to certain anticancer drugs after thawing. In conclusion, our method efficiently generates LCOs that enable anticancer drug screening at the individual patient level.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81159186","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 : 2022-07-25DOI: 10.51335/organoid.2022.2.e15
Jaewon Cho, Eun-Hye Hong, Hyun-Jeong Ko
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.
{"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}
Pub Date : 2022-06-25DOI: 10.51335/organoid.2022.2.e16
Y. Che, Yong Jun Kim
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.
{"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}
Pub Date : 2022-06-25DOI: 10.51335/organoid.2022.2.e13
A. Muotri
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].
{"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}
Pub Date : 2022-05-25DOI: 10.51335/organoid.2022.2.e14
Hanbyeol Lee, Jeong Suk Im, Daejin Choi, Jieun An, Subin Kim, Seunghee Yeon, Seulgi Yoon, Dong-Hun Woo
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.
{"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}
Pub Date : 2022-05-15DOI: 10.51335/organoid.2022.2.e5
Min Jung Kim, Jaeseo Lee, Seon Ju Mun, M. Son, Jung-Hyun Kim
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.
{"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}
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