Multi-lineage Human iPSC-Derived Platforms for Disease Modeling and Drug Discovery

Human induced pluripotent stem cells (hiPSCs) provide a powerful platform for disease modeling and have unlocked new possibilities for understanding the mechanisms governing human biology, physiology, and genetics. However, hiPSC-derivatives have traditionally been utilized in two-dimensional monocultures, in contrast to the multi-systemic interactions that influence cells in the body. We will discuss recent advances in generating more complex hiPSC-based systems using three-dimensional organoids, tissue-engineering, microfluidic organ-chips, and humanized animal systems. While hiPSC differentiation still requires optimization, these next-generation multi-lineage technologies can augment the biomedical researcher’s toolkit and enable more realistic models of human tissue function. Sharma et al. review recent advances in multi-cell-lineage, hiPSC-derived platforms for disease modeling and drug screening. These complex model systems, which include organoids, assembloids, organ-chips, and tissue-engineered constructs, are more realistic representations of human tissues containing multiple cell types that interact during development, aging, and disease.