Generation of 3D-Multicellular Human iPSC-Heart Organoids for the Noninvasive Assessment of Cardiac Fibrosis

Abstract

The lack of a precise noninvasive, clinical evaluation method for cardiac fibrosis hinders the development of successful treatments that can effectively work in physiological settings, where tissues and organs are interconnected and moderating drug responses. To address this challenge and advance personalized medicine, researchers have turned to human-induced pluripotent stem (iPS) cells, which can be differentiated to resemble the human heart in terms of structure, function and cellular composition. In this chapter, we present an assay protocol that uses these iPS cells to generate heart organoids for the in vitro evaluation of cardiac fibrosis. By establishing this biological platform, we pave the way for conducting phenotype evaluation and treatment screening in a multiscale approach, aiming to discover effective interventions for the treatment of cardiac fibrosis.

Keywords: Cardiac fibrosis; Cardiac organoid; Differentiation; Fibroblasts; Heart organoid; Reactive fibrosis; Replacement fibrosis; TGFβ; hiPSCs.