Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.
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The work of M.P.L. in the area of organoid biology and technology is supported by the Swiss National Science Foundation, the European Union’s Horizon 2020 research and innovation programme (INTENS 668294), the Personalized Health and Related Technologies Initiative from the ETH Board, the Vienna Science and Technology Fund and École Polytechnique Fédérale de Lausanne (EPFL). The authors are grateful to their collaborators in the organoid field, including J. Briscoe, H. Clevers, D. Duboule, A. Grapin-Botton, A. Kitcheva, J. Knoblich, A. Martinez-Arias and E. Tanaka. The authors thank the members of their laboratory for helpful discussions and apologize to all the scientists whose work they could not cite owing to space restrictions.
Nature Reviews Genetics thanks P. Arlotta, J. Wells and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Stem cell-derived or progenitor cell-derived 3D structures that, on much smaller scales, re-create important aspects of the 3D anatomy and multicellular repertoire of their physiological counterparts and that can recapitulate basic tissue-level functions.
- Adult stem cells
(ASCs). Somatic stem cells with the capacity to give rise to the terminally differentiated cells of the tissue in which they reside.
- Pluripotent stem cells
(PSCs). Stem cells that have the capacity to give rise to all the cell types of the embryo proper. PSCs include embryonic stem cells and induced PSCs.
Microfluidic cell culture device that contains perfused chambers in which living cells are arranged to simulate tissue-level and organ-level physiology.
The first identifiable event that triggers the formation of an asymmetric system from an initially homogeneous (symmetric) state.
- Reaction-diffusion mechanisms
Mathematical models that describe the dynamics of pattern formation in terms of local production and diffusion of activators and inhibitors and their interactions.
- Bistability of regulatory networks
The behaviour of biological systems in which positive and negative feedback between networks of regulatory elements results in only one of two mutually exclusive outcomes.
- Asymmetric cell division
The mechanism of cellular division by which the mother cell produces two daughter cells with different cell fates.
- Air–liquid interface
A method for cell culture that is typically used for epithelial cells and in which a porous filter is used to expose basal cell layers to the cell culture medium and external cell layers to the air.
Biomolecules that act in a concentration-dependent manner to determine cell fate choices and tissue patterning in vivo.
(NE). Derived from neuroectoderm, the ectodermal embryonic compartment that will give rise to the nervous system. From this epithelium, components of the sensory organs are also formed, as in the case of the eye. Can be considered a synonym of neuroectoderm.
- Neural retina
(NR). A multi-layered structure of the eye formed by the neuronal types responsible for light acquisition and conversion into neural signals.
- Retinal pigmented epithelium
(RPE). A pigmented epithelium attached to the outside of the neural retina in the eye. It provides nutritional support to neural retina cells.
- Ureteric epithelium
Derivative of the intermediate mesoderm that contributes to the formation of the renal collecting ducts.
- Metanephric mesenchyme
Derivative of the intermediate mesoderm that substantially contributes to the formation of the renal nephrons.
The identity of the gastric epithelium in the most distal part of the stomach, pertaining to an anatomical region that connects to the intestinal duodenum called the pyloric antrum.
The identity of the gastric epithelium in the upper curvature of the stomach, pertaining to an anatomical region called the fundus of the stomach.
Derived from the mesoderm, the middle embryonic germ layer that is formed upon gastrulation and will give rise to different adult tissues such as skeletal and cardiac muscle, smooth muscle, blood, cartilage, bones and dermis.
- Surface ectoderm
The part of the embryonic ectoderm that lines the exterior of the embryo (the surface). Derivatives of the surface ectoderm include the epidermis with associated glands (including the mammary glands), sensory receptors, the epithelium of the oral and nasal cavity with associated glands and the cornea and the lens of the eye, among others.
- Glandular tissues
Epithelial tissues that produce and release biomolecules (hormones and growth factors, among others) into the bloodstream, in external or internal body cavities.
Derived from the endoderm, the most inner embryonic germ layer formed upon gastrulation, that will give rise to internal structures such as the epithelial lining of the respiratory and gastrointestinal tracts and of the urinary system.
A process that occurs during mammalian embryonic development in which the three germ layers (ectoderm, mesoderm and endoderm) form from the epiblast and arrange in space to generate a more defined body plan of the organism.
Spherical epithelial cysts of fetal intestinal progenitors.
Invaginations of the intestinal epithelium at the base of villi, which typically host self-renewing LGR5+ intestinal stem cells and Paneth cells at their bottom.
- Optic vesicles
Embryonic epithelial vesicles evaginating from the forebrain neuroepithelium that will give rise to the optic cup. In organoids, they are the vesicular structures forming at early stages of organoid development, before the morphological changes that will give rise to the final optic cup structure.
- Personalized medicine
A medical procedure in which the therapy and/or treatment is tailored to a specific patient.
- Organoid biobanks
Collections of organoid samples, typically of human origin, that are stored for research purposes and aim to encompass a wide range of population genetic variance.
- 3R principles
A framework for more humane animal research aimed at replacing, reducing and refining animal experimentation.
Devices for the large-scale expansion of cells under controlled culture conditions.
- Sacrificial moulds
Templates used to form a structure; they are dissolved after the moulding process.
- Laser ablation
The controlled removal of portions of a material through irradiation with a laser beam.
The use of specialized 3D printing technologies to combine cells, biomolecules and biomaterials in 3D assemblies.
Devices comprising biological components (such as antibodies and enzymes, among others) and electrochemical components for the measurement of biological parameters.
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Rossi, G., Manfrin, A. & Lutolf, M.P. Progress and potential in organoid research. Nat Rev Genet 19, 671–687 (2018). https://doi.org/10.1038/s41576-018-0051-9
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