![]() We also highlight the tools and methodologies that are available for human organoid studies, in the hope that this information will lead basic biologists to consider using this emerging platform for the study of human pathophysiology.īuilding on the fundamental idea that biological mechanisms are conserved throughout evolution, biomedical research has traditionally focused on only a handful of model organisms. We emphasize the differences between the mouse and human systems, evaluating the advantages and disadvantages of animal models and human organoid models. This Review will instead discuss organoids as a novel model system for understanding human development and genetics that complements, and in the future might reduce, the use of animal models. Many excellent reviews have already described the various organoid model systems 9, 10, 11, 12, 13, 14, highlighted their relevance for disease modelling 15, 16 and outlined organoid-associated protocols 17. In this Review, we describe examples of PSC-derived and AdSC-derived organoid models that have shown great potential and promise in modelling human disease for a broad spectrum of life stages, from early development through to adulthood. However, the development of organoid technology is still in its infancy in comparison to established cell line and animal models, with challenges still to overcome. ![]() The potential of organoids to complement existing model systems and extend basic biological research, medical research and drug discovery into a more physiologically relevant human setting is becoming ever more widely appreciated. The analysis of organoid formation can thus provide valuable information about the mechanisms underlying human development and organ regeneration, highlighting their value for basic biological research in addition to their potential application in pharmaceutical drug testing and molecular medicine. One feature that is common to all organoids is that they are generated from pluripotent stem cells (PSCs) or adult stem cells (AdSCs also known as tissue stem cells) by mimicking human development or organ regeneration in vitro 9. However, organoids are unique, in that they are self-organizing, 3D culture systems that are highly similar to - and in some cases, histologically indistinguishable from - actual human organs 2, 3, 4, 5, 6, 7, 8. The emergence of human in vitro 3D cell culture approaches using stem cells from different organs has therefore received widespread attention as having the potential to overcome these limitations.Īttempts to model the biology of human organs - including the differentiation of human stem cells in 2D, in either the presence or absence of a 3D matrix bio-printing of human cells and the culture of cells in a microfluidic device (‘organ-on-a-chip’) 1 - were made prior to the emergence of organoids and have shown some potential for drug screening or human disease research. These include, for example, brain development, metabolism and the testing of drug efficacy. Furthermore, recent studies have identified biological processes that are specific to the human body and cannot be modelled in other animals. Nevertheless, extrapolating results from model systems to humans has become a major bottleneck in the drug discovery process. The common principles of animal development and organ physiology derived from this approach have led to a detailed mechanistic understanding of many human diseases. Historically, the investigation of disease mechanisms in animal models has progressed along a common discovery pipeline, whereby biological processes were initially investigated by genetic screens in invertebrates, followed by an analysis of evolutionary conservation in mammalian model systems, eventually leading to clinical translation to humans. ![]() The value of the achievements these model systems have made possible is proved by the fact that their use has become near universal in biomedical research today. The use of classical cell line and animal model systems in biomedical research during the late twentieth and early twenty-first centuries has been successful in many areas, such as improving our understanding of cellular signalling pathways, identifying potential drug targets and guiding the design of candidate drugs for pathologies including cancer and infectious disease. ![]()
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