Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids 公告 2021-05-06 02:26:15 Written By Kym Kilbourne Title: Building Consensus on Definition and Nomenclature of Hepatic, Pancreatic, and Biliary Organoids Abstract Organoid technology, as a powerful tool for studying development, disease, and regeneration, is rapidly expanding in its research field. With the continuous development of this field, there is an increasing call for clear definitions and nomenclature to describe these systems. To promote scientific communication and consistent interpretation, we revisited the concept of organoids and introduced an intuitive classification system and naming rules to describe these 3D structures. Through consensus among field experts, we propose an overarching definition and sub-classifications based on defining characteristics. Additionally, we propose guidelines for future system establishment, characterization, and benchmarking to promote standardization and validation of hepatopancreatobiliary (HPB) organoids. Finally, we discuss the main challenges faced by the clinical application of organoids. Definition of Organoids The concept of organoids has existed for decades, but its broad application has made its meaning ambiguous. To bring clarity to organoids and their research field, over 60 experts from 16 countries worldwide collaboratively defined organoids as three-dimensional structures derived from (pluripotent) stem cells, precursor cells, and/or differentiated cells that self-organize through cell-cell and cell-matrix interactions to recapitulate various aspects of native tissue architecture and function in vitro. Classification of Organoids We propose categorizing organoids into different groups based on defining characteristics, including epithelial organoids, multi-tissue organoids, and multi-organ organoids. Epithelial organoids are the most widely studied type, originating from a single germ layer (endoderm, mesoderm, or ectoderm) and possessing self-renewal capabilities under appropriate culture conditions. Multi-tissue organoids are established through the co-culture of cells from at least two germ layers or the co-differentiation of pluripotent stem cells (PSCs). Multi-organ organoids are the most complex and least described type of organoid, characterized by inter-organ developmental self-organization patterns. HPB Organoids from Pluripotent Stem Cells Since Yamanaka and colleagues reported the efficient reprogramming of mature somatic cells into iPSCs, numerous protocols have been developed to guide the differentiation of iPSCs into specific cell types. Now, epithelial, multi-tissue, and multi-organ HPB organoids can be generated from iPSCs. These techniques can also be applied to embryonic stem cells (ESCs), although their use is more limited due to ethical issues. Organoids from Primary Human Liver, Pancreas, and Biliary Tract Tissues Self-renewing epithelial organoids can now be cultured from primary human liver, pancreas, and biliary tract tissues. These tissue-derived epithelial organoids display a high level of genetic stability and promise fidelity to their tissue of origin, making them suitable not only for in vitro testing but also for therapeutic applications. Definition and Nomenclature of Tumor Organoids Tumor organoids are organoids derived from primary and metastatic tumors of the liver, pancreas, and biliary tract. Similar to non-tumor epithelial organoids, tumor organoids self-organize through cell-cell and cell-matrix interactions. However, unlike non-tumor organoids that recapitulate healthy tissue, tumor organoids capture the histological architecture of the original tumor and retain the genomic landscape, gene expression profile, and tumorigenic potential of the original tumor. Standardization and Validation of HPB Organoids To promote the standardization and validation of organoid systems, we propose a set of guidelines, including well-defined reproducible culture conditions, demonstration of suspected cell origins, characterization of organoid systems at the morphological, gene expression, and functional levels, and benchmarking against original tissues and cells. Clinical Applications of Organoids (Challenges and Solutions) Organoid technology holds great potential in treating many intractable diseases and can be used as advanced therapy medicinal products (ATMPs) through the injection or transplantation of cells as organoid grafts. However, before translating organoid technology from the lab to the clinic as a cell therapy, several challenges must be overcome, including the elimination of animal-derived materials, scaling up organoids to clinically relevant numbers, and overcoming post-transplant immune rejection of organoids. Conclusion As organoid technology continues to advance, our ability to describe these complex 3D systems must also improve. Consistent nomenclature and precise language are needed for effective scientific communication among researchers, enabling reproducibility and scientific progress. Here, we have developed an intuitive classification system and naming rules for HPB organoids through consensus among field experts and propose guidelines that researchers should follow when establishing new organoid systems. We view this process as interactive and dynamic, stimulating scientific discourse and comprehensive understanding of HPB organoids. We believe that similar processes will help unify and advance other fields. Kym Kilbourne
Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids 公告 2021-05-06 02:26:15 Written By Kym Kilbourne Title: Building Consensus on Definition and Nomenclature of Hepatic, Pancreatic, and Biliary Organoids Abstract Organoid technology, as a powerful tool for studying development, disease, and regeneration, is rapidly expanding in its research field. With the continuous development of this field, there is an increasing call for clear definitions and nomenclature to describe these systems. To promote scientific communication and consistent interpretation, we revisited the concept of organoids and introduced an intuitive classification system and naming rules to describe these 3D structures. Through consensus among field experts, we propose an overarching definition and sub-classifications based on defining characteristics. Additionally, we propose guidelines for future system establishment, characterization, and benchmarking to promote standardization and validation of hepatopancreatobiliary (HPB) organoids. Finally, we discuss the main challenges faced by the clinical application of organoids. Definition of Organoids The concept of organoids has existed for decades, but its broad application has made its meaning ambiguous. To bring clarity to organoids and their research field, over 60 experts from 16 countries worldwide collaboratively defined organoids as three-dimensional structures derived from (pluripotent) stem cells, precursor cells, and/or differentiated cells that self-organize through cell-cell and cell-matrix interactions to recapitulate various aspects of native tissue architecture and function in vitro. Classification of Organoids We propose categorizing organoids into different groups based on defining characteristics, including epithelial organoids, multi-tissue organoids, and multi-organ organoids. Epithelial organoids are the most widely studied type, originating from a single germ layer (endoderm, mesoderm, or ectoderm) and possessing self-renewal capabilities under appropriate culture conditions. Multi-tissue organoids are established through the co-culture of cells from at least two germ layers or the co-differentiation of pluripotent stem cells (PSCs). Multi-organ organoids are the most complex and least described type of organoid, characterized by inter-organ developmental self-organization patterns. HPB Organoids from Pluripotent Stem Cells Since Yamanaka and colleagues reported the efficient reprogramming of mature somatic cells into iPSCs, numerous protocols have been developed to guide the differentiation of iPSCs into specific cell types. Now, epithelial, multi-tissue, and multi-organ HPB organoids can be generated from iPSCs. These techniques can also be applied to embryonic stem cells (ESCs), although their use is more limited due to ethical issues. Organoids from Primary Human Liver, Pancreas, and Biliary Tract Tissues Self-renewing epithelial organoids can now be cultured from primary human liver, pancreas, and biliary tract tissues. These tissue-derived epithelial organoids display a high level of genetic stability and promise fidelity to their tissue of origin, making them suitable not only for in vitro testing but also for therapeutic applications. Definition and Nomenclature of Tumor Organoids Tumor organoids are organoids derived from primary and metastatic tumors of the liver, pancreas, and biliary tract. Similar to non-tumor epithelial organoids, tumor organoids self-organize through cell-cell and cell-matrix interactions. However, unlike non-tumor organoids that recapitulate healthy tissue, tumor organoids capture the histological architecture of the original tumor and retain the genomic landscape, gene expression profile, and tumorigenic potential of the original tumor. Standardization and Validation of HPB Organoids To promote the standardization and validation of organoid systems, we propose a set of guidelines, including well-defined reproducible culture conditions, demonstration of suspected cell origins, characterization of organoid systems at the morphological, gene expression, and functional levels, and benchmarking against original tissues and cells. Clinical Applications of Organoids (Challenges and Solutions) Organoid technology holds great potential in treating many intractable diseases and can be used as advanced therapy medicinal products (ATMPs) through the injection or transplantation of cells as organoid grafts. However, before translating organoid technology from the lab to the clinic as a cell therapy, several challenges must be overcome, including the elimination of animal-derived materials, scaling up organoids to clinically relevant numbers, and overcoming post-transplant immune rejection of organoids. Conclusion As organoid technology continues to advance, our ability to describe these complex 3D systems must also improve. Consistent nomenclature and precise language are needed for effective scientific communication among researchers, enabling reproducibility and scientific progress. Here, we have developed an intuitive classification system and naming rules for HPB organoids through consensus among field experts and propose guidelines that researchers should follow when establishing new organoid systems. We view this process as interactive and dynamic, stimulating scientific discourse and comprehensive understanding of HPB organoids. We believe that similar processes will help unify and advance other fields. Kym Kilbourne
