Organoids as an in vitro model of human development and disease

Organoids as an in vitro model of human development and disease

MARCH 2016 | Aliya Fatehullah, Si Hui Tan and Nick Barker
Organoids are three-dimensional in vitro models that closely mimic the structure and function of human tissues, offering a powerful tool for studying development, disease, and therapeutic applications. This review discusses the current state, challenges, and potential of organoid technology, emphasizing its role in both basic research and clinical applications. Organoids are derived from primary tissues, embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs), and possess the ability to self-renew and self-organize, resembling the functionality of their tissue of origin. Unlike traditional 2D cultures, organoids closely resemble primary tissues in composition and architecture, containing self-renewing stem cells that generate all major cell lineages. They can be expanded indefinitely, cryopreserved, and manipulated using techniques similar to those used in 2D cultures. The absence of mesenchymal and immune cells in most organoids allows for a reductionist approach to studying specific tissues without confounding influences from the local microenvironment. Organoids serve as a bridge between traditional 2D cultures and in vivo models, being more physiologically relevant and easier to manipulate than in vivo models. The development of organoid technology has been significantly advanced by the creation of the R-spondin method, which enables the long-term growth of human organoids. Organoids have been successfully generated from various tissues, including the gastrointestinal tract, liver, pancreas, lung, and brain, and have been used to model diseases such as cystic fibrosis, cancer, and neurodegenerative disorders. Organoids derived from ESCs and iPSCs allow for the study of germ layer specification and lineage differentiation, providing insights into human development and disease. They have also been used to model host-microbe interactions, drug screening, and personalized medicine, offering a valuable platform for drug discovery and therapeutic development. Despite their potential, organoids have limitations, including the absence of certain stromal components and challenges in modeling complex interactions. Efforts are ongoing to improve organoid culture systems to enhance their physiological relevance and applicability in clinical settings. Organoids represent a promising technology for studying human development, disease, and therapy, with significant implications for regenerative medicine and personalized treatment strategies.Organoids are three-dimensional in vitro models that closely mimic the structure and function of human tissues, offering a powerful tool for studying development, disease, and therapeutic applications. This review discusses the current state, challenges, and potential of organoid technology, emphasizing its role in both basic research and clinical applications. Organoids are derived from primary tissues, embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs), and possess the ability to self-renew and self-organize, resembling the functionality of their tissue of origin. Unlike traditional 2D cultures, organoids closely resemble primary tissues in composition and architecture, containing self-renewing stem cells that generate all major cell lineages. They can be expanded indefinitely, cryopreserved, and manipulated using techniques similar to those used in 2D cultures. The absence of mesenchymal and immune cells in most organoids allows for a reductionist approach to studying specific tissues without confounding influences from the local microenvironment. Organoids serve as a bridge between traditional 2D cultures and in vivo models, being more physiologically relevant and easier to manipulate than in vivo models. The development of organoid technology has been significantly advanced by the creation of the R-spondin method, which enables the long-term growth of human organoids. Organoids have been successfully generated from various tissues, including the gastrointestinal tract, liver, pancreas, lung, and brain, and have been used to model diseases such as cystic fibrosis, cancer, and neurodegenerative disorders. Organoids derived from ESCs and iPSCs allow for the study of germ layer specification and lineage differentiation, providing insights into human development and disease. They have also been used to model host-microbe interactions, drug screening, and personalized medicine, offering a valuable platform for drug discovery and therapeutic development. Despite their potential, organoids have limitations, including the absence of certain stromal components and challenges in modeling complex interactions. Efforts are ongoing to improve organoid culture systems to enhance their physiological relevance and applicability in clinical settings. Organoids represent a promising technology for studying human development, disease, and therapy, with significant implications for regenerative medicine and personalized treatment strategies.
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