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Everything You Always Wanted to Know About Organoid-Based Models (and Never Dared to Ask)

2022; Elsevier BV; Volume: 14; Issue: 2 Linguagem: Inglês

10.1016/j.jcmgh.2022.04.012

2352-345X

Isabelle Hautefort, Martina Poletti, Diana Papp, Tamás Korcsmáros,

Science, Research, and Medicine

Homeostatic functions of a living tissue, such as the gastrointestinal tract, rely on highly sophisticated and finely tuned cell-to-cell interactions. These crosstalks evolve and continuously are refined as the tissue develops and give rise to specialized cells performing general and tissue-specific functions. To study these systems, stem cell–based in vitro models, often called organoids, and non–stem cell–based primary cell aggregates (called spheroids) appeared just over a decade ago. These models still are evolving and gaining complexity, making them the state-of-the-art models for studying cellular crosstalk in the gastrointestinal tract, and to investigate digestive pathologies, such as inflammatory bowel disease, colorectal cancer, and liver diseases. However, the use of organoid- or spheroid-based models to recapitulate in vitro the highly complex structure of in vivo tissue remains challenging, and mainly restricted to expert developmental cell biologists. Here, we condense the founding knowledge and key literature information that scientists adopting the organoid technology for the first time need to consider when using these models for novel biological questions. We also include information that current organoid/spheroid users could use to add to increase the complexity to their existing models. We highlight the current and prospective evolution of these models through bridging stem cell biology with biomaterial and scaffold engineering research areas. Linking these complementary fields will increase the in vitro mimicry of in vivo tissue, and potentially lead to more successful translational biomedical applications. Deepening our understanding of the nature and dynamic fine-tuning of intercellular crosstalks will enable identifying novel signaling targets for new or repurposed therapeutics used in many multifactorial diseases. Homeostatic functions of a living tissue, such as the gastrointestinal tract, rely on highly sophisticated and finely tuned cell-to-cell interactions. These crosstalks evolve and continuously are refined as the tissue develops and give rise to specialized cells performing general and tissue-specific functions. To study these systems, stem cell–based in vitro models, often called organoids, and non–stem cell–based primary cell aggregates (called spheroids) appeared just over a decade ago. These models still are evolving and gaining complexity, making them the state-of-the-art models for studying cellular crosstalk in the gastrointestinal tract, and to investigate digestive pathologies, such as inflammatory bowel disease, colorectal cancer, and liver diseases. However, the use of organoid- or spheroid-based models to recapitulate in vitro the highly complex structure of in vivo tissue remains challenging, and mainly restricted to expert developmental cell biologists. Here, we condense the founding knowledge and key literature information that scientists adopting the organoid technology for the first time need to consider when using these models for novel biological questions. We also include information that current organoid/spheroid users could use to add to increase the complexity to their existing models. We highlight the current and prospective evolution of these models through bridging stem cell biology with biomaterial and scaffold engineering research areas. Linking these complementary fields will increase the in vitro mimicry of in vivo tissue, and potentially lead to more successful translational biomedical applications. Deepening our understanding of the nature and dynamic fine-tuning of intercellular crosstalks will enable identifying novel signaling targets for new or repurposed therapeutics used in many multifactorial diseases. SummaryAlthough revolutionary and increasingly used, organoids remain a challenging model for new users. In this review, we provide a general introduction for improving the accessibility to these models. We highlight areas for cross-disciplinary collaboration with biomaterial, tissue engineering, and nanofabrication sciences to broaden the application of organoids. Although revolutionary and increasingly used, organoids remain a challenging model for new users. In this review, we provide a general introduction for improving the accessibility to these models. We highlight areas for cross-disciplinary collaboration with biomaterial, tissue engineering, and nanofabrication sciences to broaden the application of organoids. The sophistication and functioning complexity of all different organs in human beings are fascinating and yet so challenging to accurately define and investigate. Decoding the complex molecular and cellular interactions taking place in each organ, and how they malfunction in diseases, is instrumental to the progress of biomedical research and eventually to personalized medicine. Previously established in vitro models (cell lines, primary cell cultures) were either too simplified or not translatable to human beings and had limitations in recapitulating the different cell types and their interactions. Scientists have had to re-explore embryology and tissue development to devise and develop novel stem cell–based in vitro models that allow studying the mechanism of the vast range of interactions taking place within an organ in health and disease. The complexity of a functional organ resides mainly in the fact that all its cells sense, adapt, and respond to their immediate and distant environments. In the gastrointestinal tract (GIT), this includes not only external factors (eg, diet, microbes1Freire R. Ingano L. Serena G. Cetinbas M. Anselmo A. 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