Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Physiological Calcium Combined with Electrical Pacing accelerates Maturation of Human Engineered Heart Tissue

ABSTRACT: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have wide potential application in basic research, drug discovery, and regenerative medicine, but functional maturation remains challenging. Here, we present a simple method whereby maturation of hiPSC-CMs can be accelerated by simultaneous application of physiological Ca 2+ and frequency-ramped electrical pacing in culture. This combination produces realistic force-frequency relationship, physiological twitch kinetics, robust β-adrenergic response, improved Ca 2+ handling, and cardiac troponin I expression within 25 days. This study provides insights into the role of Ca 2+ in hiPSC-CM maturation and offers a scalable platform for translational and clinical research.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201437 | GEO | 2022/04/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Circulating traveling waves rapidly pace and mature hiPSC-derived cardiomyocytes in self-organized tissue ring

Project description:Directed differentiation methods allow acquisition of high-purity cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes have been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSC-derived CMs can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, traveling waves (TWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with TW training show matured features including structural organization, increased cardiac-specific gene expression, enhanced Ca2+-handling properties, an increased oxygen-consumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the TWs within the SOTRs. The TW could also potentially be used for pacing the electrical excitable cells such as neuron and retina cells for various applications.

2020-02-05 | GSE140466 | GEO

Physiological Calcium Combined with Electrical Pacing accelerates Maturation of Human Engineered Heart Tissue

Project description:Physiological Calcium Combined with Electrical Pacing accelerates Maturation of Human Engineered Heart Tissue

| PRJNA831794 | ENA

Glycogen Synthase Kinase-3 Inhibition and Insulin Synergistically Enhance Proliferation and Inhibit Maturation of Human iPSC-derived Cardiomyocytes via TCF and FOXO Signaling

Project description:Embryonic signaling pathways exert stage-specific effects during cardiac development, yet the precise cues for proliferation or maturation remain elusive. To address this, we utilized spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) at day 12 of differentiation and performed a combinatory screen for various dosages of the glycogen synthase kinase-3 (GSK3) inhibitor CHIR99021 and Insulin for the analysis of cell cycle in hiPSC-CMs. Our combinatory screen for proliferation, subsequential downstream sarcomere development and RNA-seq analyses for Insulin/Akt and CHIR99021/Wnt demonstrate synergistic effects on proliferation of immature hiPSC-CMs. Conversely, removal of the Wnt and Insulin stimuli leads to rapid cell cycle exit and facilitates the terminal differentiation of immature hiPSC-CMs. Detailed characterization reveals that Wnt/CHIR99021, but not Insulin, regulates sarcomere homeostasis and architecture of immature hiPSC-CMs. Moreover, we further identify a temporal interplay between CHIR99021/Wnt via TCF and Insulin via FoxO signaling as regulators between proliferation and maturation in immature hiPSC-CMs. This work describes the cues that control proliferation versus terminal differentiation in functional immature hiPSC-CMs, and provides molecular mechanistic understanding between proliferation and maturation development of hiPSC-CMs.

2024-12-10 | GSE278598 | GEO

Dual inhibition of MAPK and PI3K/AKT pathways enhances maturation of human iPSC-derived cardiomyocytes

Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide great opportunities for mechanistic dissection of human cardiac pathophysiology; however, hiPSC-CMs remain immature relative to the adult heart. To identify novel signaling pathways driving the maturation process during heart development, we analyzed published transcriptional and epigenetic datasets from hiPSC-CMs, prenatal and postnatal human hearts. These analyses revealed that several components of the MAPK and PI3K-AKT pathways are downregulated in the postnatal heart. Here, we show that dual inhibition of these pathways for only 5 days significantly enhances the maturation of day-30 hiPSC-CMs in many domains: hypertrophy, multinucleation, metabolism, t-tubule density, calcium handling, and electrophysiology, many equivalent to day-60 hiPSC-CMs. These data indicate that the MAPK/PI3K/AKT pathways are involved in cardiomyocyte maturation and provide proof-of-concept for the manipulation of key signaling pathways for optimal hiPSC-CM maturation, a critical aspect of faithful in vitro modeling of cardiac pathologies and subsequent drug discovery.

2022-08-04 | GSE187308 | GEO

Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems

Project description:Human iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and cardiac regeneration. Challenges with quality, inter-batch consistency, cryopreservation and scale remain, reducing experimental reproducibility and clinical translation. Here, we report a robust stirred suspension cardiac differentiation protocol with careful functional characterization of the resulting hiPSC-CMs. In a bioreactor, the protocol produced 1.2E6/mL hiPSC-CMs with ～94% purity from 14 iPSC lines. Bioreactor-differentiated CMs (bCMs) showed high viability after cryo-recovery (>90%) and predominantly ventricular identity. Compared to standard monolayer-differentiated CMs (mCMs), bCMs had greater reproducibility and more mature functional properties, including pacing capture to 4 Hz and greater force production in 3D engineered heart tissues. In more readily available magnetically stirred spinner flasks, the protocol yielded 1.8E6/mL spinner-differentiated CMs (sCMs) with 94% purity. Differentiation scaled readily in spinner flasks, as a 3.8-fold increase in cultured volume yielded 3.4E6/ml sCMs. sCMs had intermediate functional properties between mCMs and bCMs. Minor protocol modifications generated the first bioreactor-derived cardiac organoids (bCOs) fully generated in suspension. These reproducible, scalable, and resource efficient approaches to generate cardiac cells and organoids with well-characterized properties will expand the applications of hiPSC-CMs.

2024-06-05 | GSE263372 | GEO

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Project description:Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening.

2020-05-26 | GSE116464 | GEO

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

2020-05-26 | GSE147694 | GEO

Human iPSC-derived closed-loop cardiac tissue for drug assessment

Project description:Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a Traveling Wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines. The TW-paced cardiomyocytes demonstrated heightened sarcomeric and functional maturation, exhibiting enhanced response to isoproterenol. Moreover, these cells showcased diminished sensitivity to verapamil and maintained low arrhythmia rates with ranolazine—two drugs associated with a low risk of torsades de pointes (TdP). Notably, the TW group displayed increased arrhythmia rates with high and intermediate risk TdP drugs (quinidine and pimozide), underscoring the potential utility of this system in drug assessment applications..

2024-01-07 | GSE251914 | GEO

RNA-Seq transcriptome profiling of human iPS cell-derived cardiomyocytes (hiPSC-CMs) following overexpression (OE) of estrogen-related receptor gamma (ERRg)

Project description:Transcriptional regulatory circuits that drive cardiomyocyte maturation are poorly understood. Human iPS cell-derived cardiomyocytes (hiPSC-CMs) have been shown to have fetal cardiomyocyte features in terms of metabolic gene expression profiles. Here we found that in hiPSC-CMs, overexpression of estrogen-related receptor gamma (ERRg) is sufficient to drive cardiomyocyte metabolic maturation programs including the induction of a number of oxidative mitochondrial metabolic genes.

2022-02-16 | GSE165966 | GEO

Activation of ERRγ enhances mitochondrial and sarcomere maturation in human induced pluripotent stem cell-derived cardiomyocytes

Project description:We identified two cardiac maturation stimulators from 9,048 compounds using Troponin I1 (TNNI1) and Troponin I3 (TNNI3) double reporter hiPSC-derived CMs. An estrogen-related receptor gamma (ERRγ)-specific agonist increased the size of hiPSC-CMs and their mitochondrial content and enhanced their mitochondrial function. In addition, combination of this agonist with an inhibitor of S-phase kinase-associated protein 2 (SKP2) increased the TNNI3 expression more highly than previous methods and enhanced cardiac maturation-related gene expression profiles.

2021-04-19 | GSE135319 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data