Abstract
The substantial progress of the human induced pluripotent stem cell (hiPSC) technologies over the last decade has provided us with new opportunities for cardiovascular drug discovery, regenerative medicine, and disease modeling. The combination of hiPSC with 3D culture techniques offers numerous advantages for generating and studying physiological and pathophysiological cardiac models. Cells grown in 3D can overcome many limitations of 2D cell cultures and animal models. Furthermore, it enables the investigation in an architecturally appropriate, complex cellular environment in vitro. Yet, generation and study of cardiac organoids—which may contain versatile cardiovascular cell types differentiated from hiPSC—remain a challenge. The large-scale and high-throughput applications require accurate and standardised models with highly automated processes in culturing, imaging and data collection. Besides the compound spatial structure of organoids, their biological processes also possess different temporal dynamics which require other methods and technologies to detect them. In this review, we summarise the possibilities and challenges of acquiring relevant information from 3D cardiovascular models. We focus on the opportunities during different time-scale processes in dynamic pharmacological experiments and discuss the putative steps toward one-size-fits-all assays.
Highlights
The substantial progress of the human induced pluripotent stem cell technologies over the last decade has provided us with new opportunities for cardiovascular drug discovery, regenerative medicine, and disease modeling
Generation and study of cardiac organoids—which may contain versatile cardiovascular cell types differentiated from human induced pluripotent stem cell (hiPSC)—remain a challenge
We summarise the possibilities and challenges of acquiring relevant information from 3D cardiovascular models
Summary
The human heart is a complex organ with multiple cell types, including cardiomyocytes, fibroblasts, endothelial cells and perivascular cells, scaffolded by extracellular matrix (ECM) (Pinto et al, 2016). One can gather samples during interventions such as coronary artery bypass surgery, valve replacement, closure of ventricular or atrial septal defects and cardiomyotomy (Lal et al, 2015) These serve as excellent sources of ethically-sourced myocardial samples of end-stage failing hearts. Examination of explanted heart samples represents a platform for identifying and optimising heart disease treatment strategies and developing better diagnostic tools (Song et al, 2014). This approach is not suitable to handle a large number of samples (Tudorache et al, 2013) or for long-term experiments (Harding et al, 1992).
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