Induced pluripotent stem cells in disease modelling and drug discovery

Nat Rev Genet. 2019 Jul;20(7):377-388. doi: 10.1038/s41576-019-0100-z.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Chimera / genetics
  • Chimera / immunology
  • Communicable Diseases / genetics
  • Communicable Diseases / immunology
  • Communicable Diseases / pathology
  • Communicable Diseases / therapy*
  • Drug Discovery / methods
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / immunology
  • Genetic Diseases, Inborn / pathology
  • Genetic Diseases, Inborn / therapy*
  • Genetic Therapy / methods
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / immunology
  • Induced Pluripotent Stem Cells / transplantation
  • Models, Animal
  • Models, Biological*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Organoids / cytology
  • Organoids / drug effects
  • Organoids / immunology
  • Tissue Engineering / methods*
  • Tissue Transplantation / methods
  • Transplantation, Heterologous