iPSC-Derived 3D Cardiac MPS Evaluation Services
ProNAMs provides cardiac evaluation services using human iPSC-derived 3D cardiac microphysiological systems (MPS). We prepare and characterize the cardiac tissue, design the study, and analyze and report the data. Perfusion-based culture and recording are delivered through an established third-party collaboration operating commercially available MPS platforms.
Unanticipated cardiotoxicity remains a significant cause of attrition in drug development, and cardiac liabilities that emerge late are expensive to discover. Human iPSC-derived cardiomyocytes give access to human cardiac electrophysiology in vitro, and 3D culture under perfusion adds tissue-level organization and continuous medium exchange that static monolayer formats do not provide.
Our cardiac evaluation platform is a medium-to-low throughput system suited to mechanistic investigation and confirmatory evaluation of a limited number of compounds, and to comparing responses under perfused versus static conditions. Findings from this platform inform internal decision-making and mechanistic understanding.
Service Model and Platform Configuration
ProNAMs is responsible for study design, iPSC differentiation and cardiac tissue preparation, endpoint definition, data analysis and reporting. Perfusion-based culture and instrumented recording are performed by our collaboration partner on commercially available MPS platforms.
Studies use iPSC-derived cardiomyocytes combined with cardiac fibroblasts and endothelial cells. Under perfused conditions, the endothelial component provides a cellular interface between the perfused compartment and the cardiac tissue. Compound access across that interface is treated as a study variable to be measured rather than an assumed improvement in physiological relevance - see the note on exposure under Model Limitations.
Studies run on a single iPSC background by default, including isogenic configurations where the design requires a matched comparison. A single background reduces one source of variability, which suits mechanistic work and comparative compound evaluation. Where the question concerns variation in response across genetic backgrounds, a multi-background design is the appropriate choice.
Capabilities
Cardiac Tissue Preparation and Characterization
iPSC differentiation to cardiomyocytes with supporting cell types, 3D tissue assembly, and characterization of purity, marker expression and baseline function before study entry.
Optical Functional Endpoints
Membrane potential, calcium handling and contractile parameters acquired by optical methods on static or perfused tissues, without terminating the preparation.
Perfused Culture and Field Potential Recording
Delivered through the collaboration where the design requires flow conditions or microelectrode array recording.
Exposure Quantification
Compound concentration in the tissue compartment and medium measured by LC-MS/MS, so that responses can be interpreted against measured rather than nominal exposure.
Model Limitations
At ProNAMs, we believe scientific rigor requires absolute transparency. A common, yet rarely discussed challenge across microphysiological systems is the discrepancy between nominal dose and actual cellular exposure. We proactively address it to protect the integrity of data.
Exposure and Data Interpretation
Compound concentration in the culture medium is not the concentration the cardiomyocytes experience. In a perfused configuration with an endothelial interface, both the interface and the flow path affect access to the cardiac tissue. Device materials matter too - polymer components in some MPS platforms adsorb hydrophobic compounds, which can reduce free concentration substantially over a study period.
This has a direct consequence for how results are read. A weaker response in a perfused format than in a static or 2D format may reflect lower exposure at the target cell rather than a difference in biology. The two are indistinguishable unless exposure is measured.
How We Handle
Where the design involves comparison across formats, or where absolute potency matters to the decision being made, compound concentration in the tissue compartment and medium is quantified by LC-MS/MS at defined timepoints. Concentration-response relationships are then constructed against measured exposure rather than nominal dose. Where exposure is not measured - for instance in a single-format study where relative comparison across arms is sufficient - that limitation is stated in the report, and conclusions are framed accordingly.
We treat this as a design decision to be made deliberately at Stage 2, not as a detail to be resolved at analysis.
Assay Parameters and Endpoints
| Endpoint Category | Method | Parameters Reported |
|---|---|---|
| Field potential | Microelectrode array (MEA) | Beat rate, field potential duration (FPD) and rate-corrected FPD, spike amplitude, conduction velocity, and arrhythmia-like events including early afterdepolarization-like waveforms and re-entrant activity |
| Membrane potential | Optical recording using voltage-sensitive dye | Action potential duration at defined repolarization percentages (e.g. APD50, APD90), upstroke characteristics, triangulation, and beat-to-beat variability |
| Calcium handling | Optical calcium transient recording | Transient amplitude, time to peak, decay kinetics, and irregularity of successive transients |
| Contractility | Optical motion analysis | Contraction and relaxation velocity, beat interval and its variability |
| Viability and structure | Viability assays adapted to 3D format; immunostaining | Tissue viability and sarcomeric organization, as supporting rather than primary safety endpoints |
| Exposure | LC-MS/MS quantification where the design requires it | Compound concentration in the tissue compartment and perfusate |
Comparison with Other 3D Cardiac Formats
Each format answers different questions. The table describes differences rather than ranking.
| Cardiac MPS (Perfused) | iPSC-Derived Cardiac Microtissues | Engineered Heart Tissue (EHT) | |
|---|---|---|---|
| Construction | Cells assembled within a perfused device, with defined compartments and flow path | Self-organizing aggregates formed in suspension or matrix | Cells cast in hydrogel around flexible posts providing mechanical anchorage |
| Structure | Compartmentalized, with a defined interface between perfused channel and tissue | Spheroidal, with cell-type composition arising from self-organization | Anisotropic fiber alignment along the axis of mechanical load |
| Mass Transfer | Active perfusion; continuous medium exchange through the tissue | Diffusion-dependent; larger constructs develop internal gradients | Predominantly diffusion; some configurations incorporate vascular-like structures |
| Primary Functional Focus | Response under flow, exposure across a cellular interface, longitudinal functional monitoring | Developmental biology and genetic disease modelling | Contractile force measurement under defined mechanical load |
| Throughput | Low to medium. Not suited to large-scale primary screening | Higher; compatible with plate-based screening | Medium to high, depending on format |
| Principal Constraint | Device complexity, cost per data point, and limited throughput | Structural variability between constructs; internal gradients in larger aggregates | Limited representation of vascular interface and flow |
Applications
Proarrhythmic Risk Investigation
Characterization of effects on field potential and action potential duration, conduction, and calcium handling, with arrhythmia-like event detection under defined pacing conditions.
Structural Cardiotoxicity Assessment
Evaluation of contractile and structural changes over repeated or continuous exposure, within the duration limits stated above.
Cardiovascular Disease Modelling
Configuration of disease models using gene-edited or disease-background iPSC lines, including cardiomyopathy-associated variants and fibrotic phenotypes, for mechanistic investigation and compound evaluation against a defined genetic background.
Perfused Versus Static Comparison
Direct comparison of compound response under perfused and static conditions on matched tissues, with exposure measured, to characterize how format affects the observed response.
Service Workflow
Stage 1 - Scoping
A technical consultation establishes the research question and how the resulting data will be used, the endpoints required, the cell line configuration, and whether a comparative format is needed. Where the objective sits outside what this platform addresses - high-throughput ranking, or endpoints requiring systemic metabolism - we say so at this point and discuss alternatives.
Indicative duration: 3–5 business days
Stage 2 - Design & Quotation
A written protocol is prepared covering platform selection, cell line and differentiation plan, concentration series, control set, pacing regime, endpoint selection, exposure measurement approach, replicate number, and the statistical approach. The protocol is issued for client review and proceeds on sign-off.
Indicative duration: 5–10 business days
Stage 3 - Cell Sourcing & Differentiation
iPSC lines are sourced from a repository, received from the client, or drawn from an established line, and differentiated to cardiomyocytes alongside the supporting cell types. Differentiated populations are characterized for cardiomyocyte purity, marker expression, and baseline functional activity before tissue assembly. This stage is performed in-house.
Indicative duration: 8–14 weeks
Stage 4 - Tissue Assembly & System Qualification
Cardiac tissues are assembled and brought to stable baseline function. Where the design uses perfusion or field potential recording, tissues are transferred to the collaboration partner for system setup at this point. Each system is qualified against pre-defined criteria before compound exposure, including baseline beat rate stability, signal quality on the relevant recording modality, viability, endothelial layer integrity where applicable, and expected response to the positive controls.
Indicative duration: 3–7 weeks
Stage 5 - Study Execution
Compound is administered across the agreed concentration series with the defined control arms. Functional recordings are acquired at the scheduled timepoints, samples for exposure quantification are collected where the design includes it, and terminal assessments are performed at study end. Where the study spans both in-house and collaboration stages, sample chain of custody and timing are specified in the protocol.
Indicative duration: 2–6 weeks
Stage 6 - Analysis & Reporting
Recordings are processed and analyzed against the endpoints and statistical thresholds fixed in the protocol. A draft report is issued for client review covering methods, platform identity, cell line and batch characterization, results against measured exposure where applicable, and the applicability domain of the data. The final report follows one round of client comments.
Indicative duration: 15–20 business days
Browse Deliverables & Timelines
NOTE: All timelines, replicate numbers and deliverables described on this page are indicative.
Frequently Asked Questions
CiPA is the initiative developing a mechanism-based approach to proarrhythmic risk assessment, in which human iPSC-derived cardiomyocyte assays form one component alongside ion channel work and in silico modelling. The ICH S7B and E14 Q&A published in 2022 set out how in vitro and non-clinical data can be used within the regulatory framework.
Our platform generates data on the endpoints central to that framework - repolarization, conduction, calcium handling and arrhythmia-like events - under 3D conditions with perfusion where the design requires it. We position this work as mechanistic and investigative rather than as a validated regulatory assay: it supports internal decision-making, hypothesis generation, and follow-up on signals identified elsewhere. Programs requiring a formally validated proarrhythmic assay for submission should discuss that requirement at scoping so the work is positioned appropriately.
Because it changes what the numbers mean. Immature cardiomyocytes have lower IK1 density and less negative resting potential, which affects repolarization measurements; they beat spontaneously, which confounds rate-dependent parameters unless pacing is applied; and their calcium handling differs from adult myocytes, which affects the interpretation of calcium transient data. We apply pacing for rate-dependent endpoints and use maturation-directed culture conditions, but the phenotype remains distinguishable from adult ventricular tissue. Results should be read as human cardiomyocyte responses under these conditions, not as a direct proxy for adult myocardium.
Not without further evidence. A weaker signal in a more complex model can arise from lower exposure at the cardiomyocyte, a shorter observation period, or a less sensitive endpoint, as well as from genuine format-related differences in biology. Establishing which explanation applies requires measuring exposure and comparing at matched exposure, and establishing which model better predicts clinical outcome requires clinical or in vivo comparison data. Where our result diverges from a client's existing data, we report the divergence and its likely sources; we do not treat a lower signal as a basis for discounting a liability.
ProNAMs performs study design, iPSC differentiation and cardiac tissue preparation, tissue characterization, endpoint definition, data analysis and reporting. Perfusion-based culture and instrumented electrode recording are performed by our collaboration partner on commercially available MPS platforms; we do not manufacture or supply devices. The division of responsibility is set out in the study protocol.
Where a study uses only optical endpoints on static 3D tissues, the work is performed entirely in-house. Whether the collaboration stage is required depends on the endpoints selected, which is determined at scoping.
Only within the duration the tissues are maintained, which is measured in days to weeks. Toxicity that develops over months of clinical exposure - including cumulative dose-dependent toxicity characteristic of certain classes - falls outside that window. A study can characterize responses to repeated exposure across the available period, and can indicate whether functional changes accumulate over that period, but the absence of a signal within it does not establish chronic cardiac safety.
For mechanistic work and compound comparison, a single background reduces one source of variability and is the default here. Where the question is whether response varies across individuals, multiple independent backgrounds are required, and the number of backgrounds - not the number of tissues per background - determines what the data can conclude. We discuss which applies at scoping, since the two designs have different cost and timeline profiles.
No. Throughput is low to medium and cost per data point is high. The platform is applied to a limited number of candidates for mechanistic investigation or confirmatory work, typically after higher-throughput formats have narrowed the set. We can advise on a staged approach across formats.
Yes, for optical endpoints. Membrane potential, calcium transient and contractile parameters can be acquired on static 3D cardiac tissues in-house, which shortens the timeline and removes dependence on collaboration platform scheduling. Field potential recording by microelectrode array, and any endpoint that depends on flow conditions or on compound access across a perfused endothelial interface, require the perfusion configuration. We recommend the static route where the endpoints allow it, and the perfused route where the question genuinely requires flow.
Discuss Your Cardiac Evaluation Program
Contact our technical team for a project assessment covering endpoint selection, platform configuration, study design, and indicative timeline.
Schedule a Consultation