uHeart
Overview
uHeart is a miniaturized model of a functional and beating human heart on a chip developed within uBeat® Stretch Platforms.
Thanks to uBeat®, a mechanical training phase resembling the heartbeat is applied to human relevant cardiac cell populations (human induced-pluripotent stem cell derived cardiomyocytes, and fibroblasts) cultured in 3D. Within few days, the generation of a functional human cardiac tissue, spontaneously and synchronously beating is achieved.
uHeart can provide measurement of the key function of the heart to understand changes in heart beating rate, electrical activities, contractility, calcium handling and structural toxicity. uHeart is indeed able to respond to drugs in a dose-dependent fashion, as close as the human heart would do, resulting the ideal platform to screen drug cardiotoxicity.
Model Characterization
Cardiac Markers
uHeart develops as 3D microtissues, with cells elongating and connecting after 7 days in culture subjected to a “beating-like” mechanical stimulation. The typical striation of the sarcomere is maintained (Troponin I staining) and ion-channel related genes profile demonstrated an enhancement of sodium, calcium and potassium gene expression (i.e. h-ERG and fast current related genes).
Functionality
uHeart develops as a synchronously beating and functional cardiac tissues in vitro, characterized by defined electrophysiological signals and contraction patterns.
Drug responses – validation for cardiotoxicity
QT prolongation and arrhythmia detection
uHeart has been qualified for detecting drug-induced QT alterations and TdP risk by benchmarking against 12 CiPA references drugs in collaboration with Accelera S.r.l. Key electrophysiological parameters were investigated: beating period-BP, FP duration-FPD, spike amplitude-SA and onset of arrhythmic events. uHeart demonstrated 83.3% sensitivity, 100% specificity and 91.6% accuracy in detecting cardiotoxicity effects.
Contraction
uHeart has been qualified for detecting drug-induced contractility changes by benchmarking against drugs with different mode of actions. Key functional parameters were investigated: Beating Period-BP, Contraction Time-CT, Relaxation Time-RT, Contraction Duration-CD and Contraction amplitude. uHeart resulted suitable to assess chronotropic, inotropic and lusitropic effects and demonstrated a highest sensitivity to predict the outcome of drugs affecting the contractile apparatus.
Check out our poster.
Calcium Handling
uHeart has been exploited for detecting drug-induced calcium transient changes. Key functional parameters were investigated: Beating Frequency -BF, Peak amplitude –PA and time-to-peak – TTP. uHeart resulted suitable to assess chronotropic and inotropic effects of compounds based on the analysis of calcium dynamics.
Check out our publications and posters.
Cardiac models of genetic diseases
uHeart is currently being applied to model rare cardiac genetic disease in collaboration with internationally recognized opinion leaders in the cardiovascular field (FNUSA-ICRC in the context of an EU project SINERGIA; Humanitas Hospital in the context of an EU project PHOENIX). uHeart demonstrated to be a superior tool to elucidate phenotypic characteristics of genetic disorders like dilated cardiomyopathies and laminopathies, with a specific focus on the identification of mechanically regulated pathways correlating with fibrotic events and on the replication of clinically observed arrhythmic events.
Check out our posters.
Key Advantages
- Human based model
- Contains different relevant cell populations
- Returns real-time physiologically relevant cardiac electrophysiological and contractile functions
- Generates clinically relevant pharmacological responses in the Cmax range