Abstract
The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.
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Acknowledgements
The author thanks all of the research team members, trainees, collaborators and other members of the scientific community for contributing to the development of the organ chip field. The author’s work discussed here was funded by grants from DARPA, FDA, NIH, BARDA, Cancer Research United Kingdom and the Gates Foundation.
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D.E.I. holds equity in Emulate, chairs its scientific advisory board and is a member of its board of directors.
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Glossary
- Microfluidic
-
A miniaturized device containing one or more channels or chambers through which fluids flow.
- Organoids
-
Self-assembled hollow clusters of cells derived from stem cells that exhibit tissue-specific structures and functions when placed in 3D cultures.
- Clinical mimicry
-
Recapitulation of physiological, pathophysiological or therapeutic responses detected in the human body.
- Personalized medicine
-
A practice of medicine that uses data obtained from an individual patient’s cells to guide decisions regarding prevention, diagnosis or treatment of disease.
- Extracellular matrix
-
(ECM). A structural scaffold composed of multiple macromolecules that orients and supports cells in living tissues.
- Soft lithography
-
A technique for fabricating microstructures or micropatterning materials using flexible stamps moulded on surfaces etched using photolithography.
- Minibioreactor
-
A small-volume (<10 ml) cell chamber in which cells are cultured to carry out a biological reaction or process.
- Cilia
-
Moving microscopic hair-like projections found on the surfaces of cells, such as lung airway epithelial cells, that cause motions in overlying fluids or mucus.
- One Health
-
A public health approach that recognizes the importance of animal health as a key component of global disease prevention, surveillance, control and mitigation.
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Ingber, D.E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet 23, 467–491 (2022). https://doi.org/10.1038/s41576-022-00466-9
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DOI: https://doi.org/10.1038/s41576-022-00466-9