Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond

Development. 2018 Mar 8;145(5):dev156166. doi: 10.1242/dev.156166.


The advent of human induced pluripotent stem cells (iPSCs) presents unprecedented opportunities to model human diseases. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers have proven to be a relatively simple tool for exploring disease pathogenesis and underlying mechanisms. In this Spotlight article, we discuss the progress and limitations of the current 2D iPSC disease-modeling platform, as well as recent advancements in the development of human iPSC models that mimic in vivo tissues and organs at the three-dimensional (3D) level. Recent bioengineering approaches have begun to combine different 3D organoid types into a single '4D multi-organ system'. We summarize the advantages of this approach and speculate on the future role of 4D multi-organ systems in human disease modeling.

Keywords: Disease modeling; Induced pluripotent stem cells; Organ-on-chip; Organoid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioengineering / instrumentation
  • Bioengineering / methods
  • Biomimetic Materials
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Culture Techniques / trends
  • Cell Differentiation
  • Disease*
  • Extracellular Matrix / physiology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / pathology
  • Induced Pluripotent Stem Cells / physiology*
  • Models, Theoretical*
  • Organoids / cytology*
  • Tissue Scaffolds