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

TLDR

Human induced pluripotent stem cells (iPSCs) enable unprecedented disease modeling, with 2D monolayer differentiated cells providing a simple platform to study pathogenesis and mechanisms. This article reviews the progress and limitations of 2D iPSC disease models and highlights recent advances toward 3D organoid and 4D multi‑organ systems that better recapitulate in vivo tissues. Recent bioengineering efforts combine diverse 3D organoids into a single 4D multi‑organ system, offering a more physiologically relevant platform for disease modeling.

Abstract

ABSTRACT 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.