Pluripotent stem cells in disease modelling and drug discovery

Key Points Embryonic stem cells and induced pluripotent stem cells (PSCs) are increasingly used to model human disorders, as a substitute for limited animal models. National and international initiatives are currently establishing repositories of human PSCs as models for human disorders. A wide range of disorders has been successfully modelled using PSCs, including monogenic, chromosomal and complex disorders, epigenetic disorders, and disorders that appear early or late in life. A number of criteria should be considered when approaching the modelling of human disease using PSCs. In this Review, we outline certain optimal or challenging characteristics affecting the selection of disorders to be modelled. A disease model can be used to understand the mechanisms underlying the cellular, molecular and physiological phenotypes of the disease, as well as to develop new therapies to attenuate the disorder. PSC-derived cells are currently used to screen potential drug therapies for many disorders. We provide examples of drug discovery for 25 neurological disorders. Drugs identified using PSC disease models are already on their way to the clinic. The use of cultured human pluripotent stem cells (PSCs) to model human diseases has revolutionized the ways in which we study monogenic, multigenic and epigenetic disorders, by overcoming some of the limitations of animal models. PSC-based disease models are generated using various strategies and can be used for the discovery of new drugs and therapies. Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening.