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Access human iPSC-derived cardiomyocytes for contractility studies, electrophysiology and disease modelling

91探花 offered in partnership with myriamed 

 

Cardiomyocytes are responsible for the heart's essential functions, including synchronised electrical conduction, excitation-contraction coupling, and the mechanical force generation required to drive the pumping action of the myocardium. Thus, cardiomyocytes are critical for toxicology research and modelling life-threatening cardiac diseases like hypertrophic cardiomyopathy and cardiovascular disorders, such as long QT syndrome.

Historically, cardiovascular disease modelling relied on animal models, but species-specific differences in beat rates and repolarisation currents frequently fail to reliably predict human responses. Primary human cardiomyocytes are equally challenging, typically sourced from surgical discards or non-transplantable organs, their use is severely hampered by limited availability, quality, and high donor variability. Immortalised cell lines (such as H9c2, HL-1, and AC16) suffer from similar limitations, lacking electrophysiological maturity and remaining prone to genetic instability.

Human iPSC-derived cardiomyocytes overcome these limitations, providing an accessible, physiologically relevant source. Moreover, recognising their predictive accuracy, the Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative explicitly proposes integrating human iPSC-derived ventricular cardiomyocytes into international guidelines to improve the assessment of proarrhythmic risk. Human iPSC-derived cells offer a highly reliable model for CiPA-aligned electrophysiology studies, enabling cardiotoxicity assessment.

Learn more about Cardiomyocytes and explore the data

Learn more about Cardiomyocytes and explore the data

Ventricular Cardiomyocytes form confluent, electrically coupled monolayers that show spontaneous, synchronised beating by day 7

 

Upon thawing, myrCell Ventricular Cardiomyocytes rapidly acquire a robust ventricular phenotype and express key cardiac markers such as cTnT, 伪-actinin, NCX1, MYH7, and MLC2v. Derived from iPSCs and driven by precisely optimised directed differentiation protocols, these cells form functional, electrically coupled monolayers and develop spontaneous, synchronised contractions within 7 days post-thaw.

Whether used in 2D or 3D culture systems, their organised sarcomeres, synchronised beating, and metabolic maturity deliver a fully human-relevant cardiac model鈥攅ffectively bridging the gap between simple in vitro assays and complex tissue physiology.

Atrial cardiomyocytes exhibit specific ion channel and marker expression, clearly distinguishable from ventricular cells

myrcell-cardiomyocytes-rna-seq-ventricular-atrial-phenotypes

 

myrCell Atrial Cardiomyocytes exhibit a robust atrial phenotype, expressing both pan-cardiac markers (cTnT, 伪-actinin) and distinguishing chamber-specific markers including NPPA, MYH6, and KCNA5. Generated using traditional directed differentiation protocols and delivered cryopreserved, the cells form electrically coupled monolayers and develop spontaneous, synchronised contractions within days post-thaw.

When paired with myrCell Ventricular Cardiomyocytes, they provide a genetically matched toolkit for target validation, atrial-selective cardiac safety pharmacology, and modelling disease such as atrial fibrillation.

myrCell Cardiomyocytes exhibit robust functional expression of key cardiac ion channels showing functionality in 2D monolayer cultures

myrcell-ventricular-atrial-cardiomyocytes-patch-clamp-ion-channel-activity

 

Both Atrial and Ventricular Cardiomyocytes establish electrically coupled 2D monolayers and begin spontaneous, synchronised contractions within days post-thaw.

The atrial and ventricular cardiomyocyte populations display different electrophysiology patterns, including distinct ion channel profiles, with the atrial cardiomyocytes displaying a significantly shorter action potential duration compared to the ventricular cells. Both cell populations remain functionally active for approximately 50 days in 2D culture.

3D engineered heart muscle (EHM) displays spontaneous tissue contraction and exhibits functional maturation

 

Beyond standard 2D monocultures, myrCell Ventricular Cardiomyocytes have been optimised for the generation of 3D engineered heart muscle (EHM). When combined with cardiac fibroblasts in a collagen-based hydrogel, they form highly functional tissues that develop physiologically relevant contractile force and robust tissue elasticity.

By exhibiting mature force-frequency responses within this 3D architecture, the cells offer a highly predictive, human-relevant model for translational cardiovascular research and drug discovery workflows.

myrCell Ventricular Cardiomyocytes engineered with a TTN mutation for dilated cardiomyopathy (DCM) disease modelling

myrcell-ventricular-cardiomyocytes-ttn-mutation-a-actinin-ctnt-ctni-mtcox2-n-cadherin

 

Wild-type myrCell Ventricular Cardiomyocytes serve as the ideal isogenic control for CRISPR-engineered disease models, such as the genetically matched Titin (TTN) A-band mutation Ventricular Cardiomyocytes product for modelling dilated cardiomyopathy (DCM).

The use of a genetically-matched control enables the comparison between healthy functionality and disease-associated mutations while minimising genetic background variability, providing a tool for target validation and the testing of novel therapeutics.

Real-time imaging with Ventricular Cardiomyocytes engineered with a SarcPaint reporter

 

For drug discovery programs and mechanistic studies requiring real-time, quantitative structural readouts alongside contractile function, myrCell SarcPaint Ventricular Cardiomyocytes provide a robust tool for live-cell imaging.

These cells exhibit the same gene expression and functional profile as wild-type ventricular cardiomyocytes, whilst carrying a genetically encoded ACTN2-Citrine reporter (SarcPaint). This reporter provides fluorescently tagged sarcomeric 伪-actinin for continuous structural assessment without the need for fixation or immunostaining. Consequently, sarcomere structure and organisation can be readily quantified using standard image analysis platforms or AI-assisted algorithms, enabling automated, high-content screening in live cardiomyocytes.

Frequently Asked Questions (FAQs)

What is the functional role of cardiomyocytes in the heart?

As the primary contractile cells of the myocardium, cardiomyocytes account for the majority of the heart's functional tissue. Cardiomyocytes coordinate the electrical network, translating electrical action potentials into physical movement. Through a process known as excitation-contraction coupling, these cells generate the rhythmic mechanical force that is ultimately responsible for propelling blood throughout the entire circulatory system.

 

How do human iPSC-derived ventricular cardiomyocytes compare with immortalised cell lines?

While immortalised cell lines (such as H9c2 and AC16) are easy to expand, they are prone to genetic instability and lack the electrophysiological and metabolic maturity of the human heart, missing the mature structure needed to accurately replicate a human action potential. In contrast, human iPSC-derived ventricular cardiomyocytes provide a physiologically relevant, genetically stable model that expresses key cardiac markers, including cTnT, 伪-actinin, NCX1, MYL2, and MYH7, and ventricular myosin light chain (MLC2v) and displays robust functional activity, including regular beating (synchronous after 7 days)鈥 and ion channel expression, INa, ICa and IK1.

 

What is the CiPA initiative, and why are human iPSC-derived cardiomyocytes essential to its framework?

The Comprehensive in Vitro Proarrhythmia Assay (CiPA) is a global initiative established by , aimed at modernising and improving the preclinical assessment of drug-induced cardiotoxicity. Historically, international safety guidelines relied heavily on single-ion channel assays and animal models, which frequently failed to reliably predict human proarrhythmic risk. To overcome these limitations, the CiPA framework explicitly proposes integrating human iPSC-derived cardiomyocytes into standard safety evaluations. Because these cells express functional human ion channels and accurately mirror clinical electrophysiological responses, they provide a predictive in vitro model for evaluating cardiotoxicity.

 

What are the key differences between atrial and ventricular iPSC-derived cardiomyocytes?

Atrial and ventricular cardiomyocytes exhibit distinct structural and electrophysiological profiles, such as the specific expression of alpha-myosin heavy chain (alpha-MHC) in the atria and beta-MHC in the ventricles. For targeted drug discovery, ventricular cells are required to evaluate proarrhythmic risks, whereas atrial cells enable assessment of atrial fibrillation disorders and atrial-selective pharmacology.

 

References

  1. Denning C, et al. "Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform" Biochim Biophys Acta. 2016; 1863(7 Pt B):1728-48. doi: 10.1016/j.bbamcr.2015.10.014.  

  2. Onodi Z, et al. "Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype" J Mol Cell Cardiol. 2022; 165:19-30. doi: 10.1016/j.yjmcc.2021.12.007.

  3. Sala L, et al. "Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?" British Journal of Pharmacology. 2016; 174(21):3749鈥3765. doi: 10.1111/bph.13577.