ArticleJournal of molecular and cellular cardiology2018
Afterload promotes maturation of human induced pluripotent stem cell derived cardiomyocytes in engineered heart tissues.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it.
- ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure.Cardiovascular research · 2019Guideline
- Hydrogel platforms for 3D cardiac tissue engineering and fibrotic disease modelling.FEBS open bio · 2026Review
- Curved by Design: Applying Microfluidic Principles for Nonplanar and Planar Suspended Tissue Patterning to the Development of Bladder Models with Tunable Mechanics.bioRxiv : the preprint server for biology · 2026Article
- Digital Light Processing 3D Printing Enables Versatile Fabrication of Human Engineered Heart Tissues.Cell biomaterials · 2026Article
- Engineering the Cellular Microenvironment for Human Induced Pluripotent Stem Cell Cardiac Differentiation: Beyond Wnt Signaling.Bioengineering (Basel, Switzerland) · 2026Review
- Biomechanical stress unmasks a fibroblast-dependent hypercontractile-disarray phenotype in MYBPC3 truncation HCM.APL bioengineering · 2026Article
- Human iPSC-derived 3D cardiac models for cardiomyopathies: organoids, spheroids, and engineered heart tissues as translational platforms.Stem cells (Dayton, Ohio) · 2026Review
- Restoration of structural organization in engineered cardiac microtissues is promoted by cardiomyocyte beating.Communications biology · 2026Article
- Review
- Pediatric dilated cardiomyopathy caused by TNNT2-R151W mutation: Modeling and rescue in patient-derived induced pluripotent stem cells and engineered heart tissue.Bioengineering & translational medicine · 2026Article
- Dystrophin Loss in Engineered Heart Tissues Recapitulates Clinically Relevant Aspects of Dystrophic Cardiomyopathy.Journal of biomechanical engineering · 2026Article
- Article
- A Monolithic 3D-Printed Platform for Functional Maturation and In Situ Contractility Assessment of 3D Skeletal Muscle.Biomaterials research · 2026Article
- In vitro approaches to mimic cardiac mechanical load dynamics for enhancing maturation and disease modelling.Cardiovascular research · 2025Review
- Crossbow Bioreactors for Studying the Effects of Time-Varying Mechanical Preload and Afterload on Engineered Cardiac Tissues.Advanced functional materials · 2025Article
- Tapered Pillar Design for High-Precision Force Readout in Miniaturized Engineered Heart Tissues From Human Pluripotent Stem Cells.Advanced healthcare materials · 2025Article
- A Micro-Engineered Heart Tissue Model of Desmin-related Cardiomyopathy Caused by Mutant αB Crystallin.bioRxiv : the preprint server for biology · 2025Article
- Computational Simulations Show Proof-of-Concept for Optogenetic Suppression of Ectopic Activity in Cardiac Stem Cell Therapy.Cardiovascular engineering and technology · 2025Article
- Vascularized and Perfusable Human Heart-on-a-Chip Model Recapitulates Aspects of Myocardial Ischemia and Enables Analysis of Nanomedicine Delivery.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones.Stem cells (Dayton, Ohio) · 2025Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) grown in engineered heart tissue (EHT) can be used for drug screening, disease modeling, and heart repair. However, the immaturity of hiPSC-CMs currently limits their use. Because mechanical loading increases during development and facilitates cardiac maturation, we hypothesized that afterload would promote maturation of EHTs. To test this we developed a system in which EHTs are suspended between a rigid post and a flexible one, whose resistance to contraction can be modulated by applying braces of varying length. These braces allow us to adjust afterload conditions over two orders of magnitude by increasing the flexible post resistance from 0.09 up to 9.2 μN/μm. After three weeks in culture, optical tracking of post deflections revealed that auxotonic twitch forces increased in correlation with the degree of afterload, whereas twitch velocities decreased with afterload. Consequently, the power and work of the EHTs were maximal under intermediate afterloads. When studied isometrically, the inotropy of EHTs increased with afterload up to an intermediate resistance (0.45 μN/μm) and then plateaued. Applied afterload increased sarcomere length, cardiomyocyte area and elongation, which are hallmarks of maturation. Furthermore, progressively increasing the level of afterload led to improved calcium handling, increased expression of several key markers of cardiac maturation, including a shift from fetal to adult ventricular myosin heavy chain isoforms. However, at the highest afterload condition, markers of pathological hypertrophy and fibrosis were also upregulated, although the bulk tissue stiffness remained the same for all levels of applied afterload tested. Together, our results indicate that application of moderate afterloads can substantially improve the maturation of hiPSC-CMs in EHTs, while high afterload conditions may mimic certain aspects of human cardiac pathology resulting from elevated mechanical overload.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.