hPSC-derived organoids: models of human development and disease
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REVIEW
hPSC-derived organoids: models of human development and disease Tristan Frum 1 & Jason R. Spence 1,2,3 Received: 21 April 2020 / Revised: 30 June 2020 / Accepted: 18 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Organoids derived from human pluripotent stem cells (hPSCs) have emerged as important models for investigating humanspecific aspects of development and disease. Here we discuss hPSC-derived organoids through the lens of development— highlighting how stages of human development align with the development of hPSC-derived organoids in the tissue culture dish. Using hPSC-derived lung and intestinal organoids as examples, we discuss the value and application of such systems for understanding human biology, as well as strategies for enhancing organoid complexity and maturity. Keywords Stem cells . Development . Organoids . Human . Disease modeling . Cell signaling
Introduction During development, a small aggregate of pluripotent cells in the embryo are guided through a series of cell fate decisions to generate the incredible diversity of cell types required for human life. Along the way, multiple specialized cell types organize into complex 3D structures to build organs, which perform essential physiological tasks such as respiration in the lungs, nutrient absorption in the gut, and filtering of blood in the kidneys. For centuries, scientists have worked to understand the process of development and to identify the cellular and molecular cues that guide cells to generate a particular organ. Now, scientists are applying this knowledge to recapitulate development in a cell culture dish, guiding cells to organize into complex 3D models of human organ-like form and function, structures known as organoids. Organoids permit scientific investigation of human development, physiology, and disease at a scale and level of precision not previously possible. Traditionally, scientists have relied on a combination of animal models and human 2D cell culture models to investigate human biology. While these * Jason R. Spence [email protected] 1
Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA
2
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA
3
Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, USA
approaches have led to innumerable important discoveries, animal models and 2D cell culture models are not without their shortcomings. Animal models are complex, making it difficult to discern cause and effect for many experiments, provide limiting amounts of tissue for analysis, and by their nature are imperfect models of human physiology. Traditional human 2D cell culture models on the other hand are often too simple, containing a single cell type attached to the culture dish as a monolayer, or floating as single cells in suspension culture. Moreover, 2D cell culture models are typically derived from cancer or induced to a
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