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Induced pluripotent stem cells in disease modelling and drug discovery

Nature Reviews Genetics (2019) | Download Citation


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.

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The authors apologize to researchers whose studies could not be included owing to space constraints.

Reviewer information

Nature Reviews Genetics thanks J. Wu, L. Studer, C. Svendsen and other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    • R. Grant Rowe
    •  & George Q. Daley


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The authors contributed equally to all aspects of the article.

Competing interests

G.Q.D. holds intellectual property relevant to development of cell and drug therapies based on iPSC technology.

Corresponding author

Correspondence to George Q. Daley.


Induced pluripotent stem cells

(iPSCs). Pluripotent cells derived from terminally differentiated somatic cells generated by reprogramming via introduction of a defined set of transcription factors.

Directed differentiation

The use of morphogens and environmental signals to direct the state of pluripotent cells towards a desired lineage.

Cell state conversion

The process by which a cell is converted from one identity to another, frequently via the expression of exogenous transcription factors.

Tissue engineering

The synthetic recapitulation of the cellular composition and matrix structure of a target tissue.


The transplantation of cells from one species into a different species.


A growth factor or chemical signal that regulates cellular differentiation or tissue patterning.


A bacterial DNA endonuclease that uses RNAs to localize and cleave targeted sequences within a genome. This enzyme has been exploited as a technology for precise genomic editing to introduce or correct specific genetic mutations in induced pluripotent stem cells.


An experimental system in which tissue architecture and cellular composition are assembled on a fabricated synthetic matrix.

Batch effects

Variations between experimental replicates due to differences in cellular source or reagent lot.


Undifferentiated, immature haematopoietic cells. They can be either rare, normal haematopoietic progenitors within healthy haematopoietic organs or transformed leukaemic cells arrested at an early state of differentiation.


A therapeutic approach using modulation of the immune system.

Chimeric antigen receptor T cells

(CAR T cells). Genetically manipulated T cells bearing a modified T cell receptor against a specific target.

Quantitative trait loci

(QTLs). DNA sequences whose variation contributes to the manifested heterogeneity of a quantitative polygenic trait.


A term to describe two cells, tissues or organisms that have the same genotype.

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