Eiichiro Takada, Hayato L. Mizuno, Yoshiki Takeoka, Shuichi Mizuno
{"title":"经硅学和体外双向验证的特定深度区衍生软骨细胞球体和集群的形成","authors":"Eiichiro Takada, Hayato L. Mizuno, Yoshiki Takeoka, Shuichi Mizuno","doi":"10.3389/fbioe.2024.1440434","DOIUrl":null,"url":null,"abstract":"3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters <jats:italic>in vitro</jats:italic>. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation <jats:italic>in silico</jats:italic> was validated morphologically with cluster formation <jats:italic>in vitro</jats:italic> and <jats:italic>vice versa</jats:italic>. Since zone specific chondrocyte cluster models <jats:italic>in silico</jats:italic> showed similarity with corresponding <jats:italic>in vitro</jats:italic> model, the <jats:italic>in silico</jats:italic> has a potential to be used for prediction of the 3D multicellular <jats:italic>in vitro</jats:italic> models used for development, disease, and therapeutic models.","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bidirectionally validated in silico and in vitro formation of specific depth zone-derived chondrocyte spheroids and clusters\",\"authors\":\"Eiichiro Takada, Hayato L. Mizuno, Yoshiki Takeoka, Shuichi Mizuno\",\"doi\":\"10.3389/fbioe.2024.1440434\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters <jats:italic>in vitro</jats:italic>. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation <jats:italic>in silico</jats:italic> was validated morphologically with cluster formation <jats:italic>in vitro</jats:italic> and <jats:italic>vice versa</jats:italic>. Since zone specific chondrocyte cluster models <jats:italic>in silico</jats:italic> showed similarity with corresponding <jats:italic>in vitro</jats:italic> model, the <jats:italic>in silico</jats:italic> has a potential to be used for prediction of the 3D multicellular <jats:italic>in vitro</jats:italic> models used for development, disease, and therapeutic models.\",\"PeriodicalId\":12444,\"journal\":{\"name\":\"Frontiers in Bioengineering and Biotechnology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Bioengineering and Biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3389/fbioe.2024.1440434\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2024.1440434","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Bidirectionally validated in silico and in vitro formation of specific depth zone-derived chondrocyte spheroids and clusters
3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters in vitro. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation in silico was validated morphologically with cluster formation in vitro and vice versa. Since zone specific chondrocyte cluster models in silico showed similarity with corresponding in vitro model, the in silico has a potential to be used for prediction of the 3D multicellular in vitro models used for development, disease, and therapeutic models.
期刊介绍:
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.