Human stem cell-based disease modeling: prospects and challenges

Abstract

Human stem cell-based disease models have great promise to advance our understanding of human disease. These models can be derived from patients with genetic disorders and manipulated with genome editing and myriad differentiation protocols to model pathologies in vitro. However, several challenges have impeded the full potential of stem cell-based in vitro disease modeling. Many genetically predisposed diseases take time to manifest and occur in specific tissue microenvironments, and these parameters are often not adequately modeled using conventional shorter-term monolayer cultures. These challenges must be overcome especially for cases where animal models also incompletely recapitulate the complex pathologies found in humans. As prominent ways to tackle these challenges we discuss here how advanced genome editing tools in human stem cells and human organoid cultures, specifically the example of intestinal organoids, contribute genetically defined models that recapitulate phenotypes of disease.