New Modalities of 3D Pluripotent Stem Cell-Based Assays in Cardiovascular Toxicity

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.

Derivation and travelling wave analysis of phenotype-structured haptotaxis models of cancer invasion

“…We focus on a biological scenario wherein cell proliferation, cell production of MDEs and ECM degradation have a stronger impact on the dynamics of the system than haptotactic cell movement and diffusion of MDEs, which in turn have a stronger impact than random cell movement and cell phenotypic changes [4,5,33,49,67]. To this end, we introduce a small parameter ε ∈ R + * and choose the parameter scaling…”

Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models

“…36 In general, spheroids are obtained by one or multiple cell types which spontaneously form adherent cell populations with non-uniform sizes (Figure 1). 37,38 A clear distinction of organoids and spheroids is difficult, as the terms were mostly used interchangeably. 39,40 However, organoids are described as more complex 3D cell system with structures that resemble the native organ characteristics closer than spheroids.…”

“…In 1907 Harrison produced the first described spheroids by using the hanging drop method to generate cell aggregates using embryonic tissue 36 . In general, spheroids are obtained by one or multiple cell types which spontaneously form adherent cell populations with non‐uniform sizes ( Figure ) 37,38 . A clear distinction of organoids and spheroids is difficult, as the terms were mostly used interchangeably 39,40 .…”