Organoids as an in vitro model of human development and disease

Organoids as an in vitro model of human development and disease

VOLUME 18 | NUMBER 3 | MARCH 2016 | Aliya Fatehullah*, Si Hui Tan* and Nick Barker*
The in vitro organoid model is a significant technological advancement, serving as an essential tool in both basic biology and clinical applications. This near-physiological 3D model facilitates the study of various in vivo biological processes, including tissue renewal, stem cell/niche functions, and responses to drugs, mutations, or damage. The term 'organoid' encompasses 3D organotypic cultures derived from primary tissues, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), as well as whole or segmented organs. Organoids are defined as in vitro 3D cellular clusters that can self-renew and self-organize, exhibiting similar organ functionality to the tissue of origin. The development of organoid technology has been driven by advancements in understanding stem cell niches and signaling pathways that control stem cell maintenance and differentiation. The R-spondin method, which uses a combination of growth factors, has been particularly influential in generating intestinal organoids. Organoids have been successfully generated from various regions of the mouse gastrointestinal tract and have been adapted for human applications, including the generation of intestinal, gastric, liver, and pancreatic organoids. Organoids offer several advantages over traditional in vitro cultures, including their similarity to primary tissue in composition and architecture, the ability to expand indefinitely, and the lack of mesenchymal/stromal components. These features make organoids valuable for studying human development, disease, and clinical applications. They can be used for drug screening, disease modeling, and personalized medicine, providing a bridge between traditional 2D cultures and in vivo models. Despite their benefits, organoids have limitations, such as the absence of stromal components and potential challenges in drug penetration due to the rigid extracellular matrix. Future developments aim to address these limitations by optimizing culture conditions and developing more defined extracellular matrices. The growing interest in organoid technology is expected to lead to further advancements in both research and clinical applications.The in vitro organoid model is a significant technological advancement, serving as an essential tool in both basic biology and clinical applications. This near-physiological 3D model facilitates the study of various in vivo biological processes, including tissue renewal, stem cell/niche functions, and responses to drugs, mutations, or damage. The term 'organoid' encompasses 3D organotypic cultures derived from primary tissues, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), as well as whole or segmented organs. Organoids are defined as in vitro 3D cellular clusters that can self-renew and self-organize, exhibiting similar organ functionality to the tissue of origin. The development of organoid technology has been driven by advancements in understanding stem cell niches and signaling pathways that control stem cell maintenance and differentiation. The R-spondin method, which uses a combination of growth factors, has been particularly influential in generating intestinal organoids. Organoids have been successfully generated from various regions of the mouse gastrointestinal tract and have been adapted for human applications, including the generation of intestinal, gastric, liver, and pancreatic organoids. Organoids offer several advantages over traditional in vitro cultures, including their similarity to primary tissue in composition and architecture, the ability to expand indefinitely, and the lack of mesenchymal/stromal components. These features make organoids valuable for studying human development, disease, and clinical applications. They can be used for drug screening, disease modeling, and personalized medicine, providing a bridge between traditional 2D cultures and in vivo models. Despite their benefits, organoids have limitations, such as the absence of stromal components and potential challenges in drug penetration due to the rigid extracellular matrix. Future developments aim to address these limitations by optimizing culture conditions and developing more defined extracellular matrices. The growing interest in organoid technology is expected to lead to further advancements in both research and clinical applications.
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