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R E V I E W SERIES ON STEM CELL BIOLOGYSERIES ON STEM CELL BIOLOGY Organoids as an in vitro model of human development and disease 1 1 1,2,3, Aliya Fatehullah , Si Hui Tan and Nick Barker * The in vitro organoid model is a major technological breakthrough that has already been established as an essential tool in many basic biology and clinical applications. This near-physiological 3D model facilitates an accurate study of a range of in vivo biological processes including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage. In this Review, we discuss the current achievements, challenges and potential applications of this technique. The successful exploitation of human stem cells for clinical use has long lack mesenchyme/stroma provides a reductionist approach for studying been hampered by our inability to maintain and expand adult stem cells the tissue type of interest without confounding influences from the local while retaining their multi-lineage potential in vitro. However, advances microenvironment. Organoids represent an important bridge between in our understanding of stem cell niches and the role of key signalling traditional 2D cultures and in vivo mouse/human models, as they are modulators in controlling stem cell maintenance and differentiation more physiologically relevant than monolayer culture models and are far have fuelled the development of new 3D in vitro culture technologies more amenable to manipulation of niche components, signalling path- that sustain stem-cell-driven formation of near-physiological, self- ways and genome editing than in vivo models (Table 1).