Cardiac Efficacy Testing and Disease Modeling
Measure therapeutic responses in human 3D cardiac microtissues and develop disease-relevant models tailored to your program.
Move from compound exposure to a measurable cardiac response. SmartHeart combines human iPSC-derived cardiomyocytes, cardiac fibroblasts and tissue-level mechanics in a 96-well format to quantify how a treatment changes contraction, relaxation and rhythm.
Use the platform for cardiac efficacy studies, or partner with us to develop a fit-for-purpose model of hypertrophic remodeling or dilated cardiomyopathy around your biology and therapeutic question.
Human 3D cardiac microtissues translate tissue deformation into quantitative functional endpoints.
MEASURE THE RESPONSE THAT MATTERS
SmartHeart captures direct changes in cardiac function, helping teams compare candidates, concentrations and controls with endpoints that sit closer to the therapeutic phenotype than molecular readouts alone.
Contractile response
Quantify contraction amplitude and derived strain or stress across concentration- or time-response designs.
Rate and rythm
Track beating frequency, regularity and treatment-induced instability at tissue level.
Relaxation kinetics
Detect changes in contraction and relaxation speed or timing that may reveal lusitropic effects.
Mechanistic context
Add optical calcium, action-potential, imaging or molecular readouts when the study question requires them.
SmartHeart's qualified core workflow identified positive and negative inotropic responses across seven reference compounds.
Additional endpoints are selected and characterized for each study design.
FROM EFFICACY TESTING TO DISEASE-RELEVANT RESCUE
Efficacy studies
Measure dose response, onset, reversibility and therapeutic window in a defined tissue context; add mechanistic endpoints when needed.
Disease-model development
Establish a reproducible disease-control difference, then build a fit-for-purpose assay to test therapeutic rescue.
DEVELOP THE CARDIAC DISEASE MODEL YOUR PROGRAM NEEDS
Disease modeling is not one protocol applied to every indication. We start with the causal biology, define the expected phenotype and design a study that can distinguish disease from control, and rescue from noise.
HYPERTROPHIC REMODELING
SmartHeart could be adapted to study hypercontractility, impaired relaxation and progressive structural remodeling using disease-relevant cells or controlled pro-hypertrophic stimulation. A project would combine functional endpoints with orthogonal evidence of hypertrophy.
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Potential strategies: patient-derived or isogenic HCM cells; gene-edited variants; chronic neurohumoral or mechanical challenge.
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Priority readouts: contraction amplitude, relaxation kinetics, beat regularity, calcium handling, tissue morphology and cardiomyocyte size.
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Therapeutic question: does treatment normalize the phenotype without suppressing viability or baseline function?
DILATED CARDIOMYOPATHY
For DCM, the objective would be to reproduce a stable hypocontractile or stress-sensitive phenotype and quantify functional rescue. Genetic programs could include LMNA-, TTN- or BAG3-related disease, subject to cell-line feasibility and assay development.
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Potential strategies: patient-derived cells, CRISPR-engineered variants or disease-relevant stress conditions with matched controls.
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Priority readouts: contractile deficit, kinetics, rhythm stability, calcium handling, tissue integrity and mechanism-specific biomarkers.
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Therapeutic question: does the intervention restore function, and is the rescue consistent with the intended mechanism?
Conceptual illustration, not experimental data
CASE STUDY REVEALING A FUNCTIONAL RESCUE MECHANISM IN LMNA CARDIOMYOPATHY
A published study using 4Dcell's ring-shaped cardiac microtissue architecture shows how a human 3D model can connect a pathogenic variant to organelle dysfunction, impaired contraction and pharmacological rescue.
THE CHALLENGE
LMNA-related cardiomyopathy can lead to severe electrical and mechanical dysfunction, yet the pathway from nuclear-envelope mutation to contractile failure remains difficult to resolve in conventional cell culture.
THE MODEL
Researchers compared patient-derived hiPSC cardiomyocytes carrying the LMNA p.H222P variant with a CRISPR-corrected isogenic control. The cells showed comparable cardiac differentiation and sarcomere organization, allowing the team to interrogate functional and metabolic differences in 3D cardiac tissues.
WHAT THE MODEL REVEALED
Researchers compared patient-derived hiPSC cardiomyocytes carrying the LMNA p.H222P variant with a CRISPR-corrected isogenic control. The cells showed comparable cardiac differentiation and sarcomere organization, allowing the team to interrogate functional and metabolic differences in 3D cardiac tissues.
Impaired mechanics
LMNA-mutant tissues displayed reduced contractile performance compared with the corrected isogenic control.
Mitochondrial deficit
Reduced MCU, an increased MICU1:MCU ratio and increased PDH phosphorylation were associated with lower respiration and ATP production.
Altered calcium
Calcium transients had higher amplitude and slower reuptake, pointing to disturbed calcium homeostasis.
Functional rescue
Amorolfine improved mitochondrial calcium uptake and contractility, linking pathway modulation to tissue-level rescue.
WHY SMARTHEART FOR A CUSTOM CARDIAC PROGRAM
Disease modeling is not one protocol applied to every indication. We start with the causal biology, define the expected phenotype and design a study that can distinguish disease from control, and rescue from noise.
Human 3D tissue
hiPSC-derived cardiomyocytes and fibroblasts self-assemble into mechanically loaded cardiac rings.
Direct function
Contraction, relaxation, rate and rhythm are measured from tissue motion rather than inferred from a surrogate.
Buil-in replication
Nine microtissues per well create multiple tissue-level observations within a standard 96-well plate.
Flexible biology
Cell source, perturbation, timing and orthogonal readouts can be selected around the disease hypothesis.