Micro-heart muscle arrays enable medium-throughput experiments to model the cardiac response to a variety of environmental and pharmaceutical effects. Here, we describe stem cell culture maintenance, methods for successful cardiac differentiation, and formation of micro-heart muscle arrays for electrophysiology and molecular biology assays.
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Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.
iScience
June 2024
Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO 63130, USA.
Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM pathogenesis. Here, we developed an physiological model to investigate how mechanics acts together with HCM-linked myosin binding protein C (MYBPC3) mutations to trigger disease. Micro-heart muscles (μHM) were engineered from induced pluripotent stem cell (iPSC)-derived cardiomyocytes bearing MYBPC3 mutations and challenged to contract against substrates of different elasticity.
View Article and Find Full Text PDFEngineered tissue geometry and Plakophilin-2 regulate electrophysiology of human iPSC-derived cardiomyocytes.
APL Bioeng
March 2024
Department of Biomedical Engineering, Washington University in St. Louis McKelvey School of Engineering, St. Louis, Missouri 63130, USA.
Engineered heart tissues have been created to study cardiac biology and disease in a setting that more closely mimics heart muscle than 2D monolayer culture. Previously published studies suggest that geometrically anisotropic micro-environments are crucial for inducing " like" physiology from immature cardiomyocytes. We hypothesized that the degree of cardiomyocyte alignment and prestress within engineered tissues is regulated by tissue geometry and, subsequently, drives electrophysiological development.
View Article and Find Full Text PDFHypertrophic cardiomyopathy is the most common cause of sudden death in the young. Because the disease exhibits variable penetrance, there are likely nongenetic factors that contribute to the manifestation of the disease phenotype. Clinically, hypertension is a major cause of morbidity and mortality in patients with HCM, suggesting a potential synergistic role for the sarcomeric mutations associated with HCM and mechanical stress on the heart.
View Article and Find Full Text PDFDynamic control of contractile resistance to iPSC-derived micro-heart muscle arrays.
J Biomed Mater Res A
April 2024
Department of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
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.
View Article and Find Full Text PDFRobust, Automated Analysis of Electrophysiology in Induced Pluripotent Stem Cell-Derived Micro-Heart Muscle for Drug Toxicity.
Tissue Eng Part C Methods
September 2022
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
Drugs are often removed from clinical trials or market progression owing to their unforeseen effects on cardiac action potential and calcium handling. Induced pluripotent stem cell-derived cardiomyocytes and tissues fabricated from these cells are promising as screening tools for early identification of these potential cardiac liabilities. In this study, we describe an automated, open-source MATLAB-based analysis software for calculating cardiac action potentials and calcium transients from fluorescent reporters.
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