Induced pluripotent stem cells in disease modelling and drug discovery

The derivation of induced pluripotent stem cells (iPSCs) over a decade ago sparked widespread enthusiasm for the development of new models of human disease, enhanced platforms for drug discovery and more widespread use of autologous cell-based therapy. Early studies using directed differentiation of iPSCs frequently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and organ-level diseases has required development of more complex, 3D, multicellular systems. Organoids and human–rodent chimaeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer. Enthusiasm for patient-specific therapies based on induced pluripotent stem cells (iPSCs) has risen in parallel with rapid advances in genome editing. This Review summarizes the progress in iPSC-based disease modelling over the past decade, with a focus on 3D organoid systems and chimeric models being exploited for new therapeutic approaches.