Key result
Elastomer-grafted iPSC-CM arrays on a magnetorheological substrate successfully elicit acute calcium and contractile changes.
Why the study?
Understanding of how mechanical forces precisely affect cardiac cellular biology remains incomplete, and previous in vitro models studying afterload often require exogenous extracellular matrix or lack dynamic control.
A novel in vitro system using magnetorheological elastomeric substrates enables the dynamic simulation of altered afterload in iPSC-derived micro-heart muscle arrays.
May advance in vitro afterload modeling in iPSC-CM systems; leaves open clinical translation pending further validation.
Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, our understanding of how mechanical forces exactly affect the cellular biology of the heart remains incomplete. In vitro models based on cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM) enable researchers to develop medium to high-throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces, such as cardiac afterload. However, most of these models require exogenous extracellular matrix (ECM) to form cardiac tissues. Recently, a system was developed to simulate changes in afterload by grafting ECM-free micro-heart muscle arrays to elastomeric substrates of discrete stiffnesses. In the present study, we extended this system by combining the elastomer-grafted tissue arrays with a magnetorheological elastomeric substrate. This system allows iPSC-CM based micro-heart muscle arrays to experience dynamic changes in contractile resistance to mimic dynamically altered afterload. Acute changes in substrate stiffness led to acute changes in the calcium dynamics and contractile forces, illustrating the system's ability to dynamically elicit changes in tissue mechanics by dynamically changing contractile resistance.
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Schuftan et al. (2023) studied Cardiovascular disease (in vitro model). Magnetorheological elastomeric substrate was evaluated on Calcium dynamics and contractile forces. An in vitro system combining elastomer-grafted iPSC-CM tissue arrays with a magnetorheological elastomeric substrate successfully elicited acute changes in calcium dynamics and contractile forces.
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