Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

TLDR

Robust and predictive in vitro models of human cardiac tissue function could transform drug testing and disease understanding, yet generating high‑fidelity adult‑like cardiac tissue analogs remains challenging. The study systematically explores design criteria for pluripotent stem cell‑derived engineered cardiac tissue. Parameters such as biomechanical stress during tissue remodeling, input‑cell composition, electrical stimulation, and tissue geometry were evaluated. A 3D matrix‑based microenvironment combined with uniaxial mechanical stress and a mix of cardiomyocytes and fibroblasts improves performance and maturation of engineered cardiac tissue.

Abstract

Significance Robust and predictive in vitro models of human cardiac tissue function could have transformative impact on our ability to test new drugs and understand cardiac disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. In this paper, we systematically explore the design criteria for pluripotent stem cell-derived engineered cardiac tissue. Parameters such as biomechanical stress during tissue remodeling, input-cell composition, electrical stimulation, and tissue geometry are evaluated. Our results suggest that a specified combination of a 3D matrix-based microenvironment, uniaxial mechanical stress, and mixtures of cardiomyocytes and fibroblasts improves the performance and maturation state of in vitro engineered cardiac tissue.