The models and assays utilized in preclinical drug development play a crucial role in determining the success of clinical trials. However, findings from 2D cell cultures or animal models often do not translate effectively to patients with neuromuscular diseases. This is primarily due to significant differences in genetics, physiology, and the complex 3D tissue environment. This challenge highlights the urgent need for in vitro systems that accurately represent human muscle physiology and function. In the context of muscle biology and diseases—such as various forms of muscular dystrophy—contractility serves as a central functional metric. This aspect cannot be fully assessed using biochemical or structural assays alone. Therefore, effective models must not only cultivate 3D muscle tissue but also demonstrate the ability to contract. Furthermore, this contraction must be measurable in a quantitative and reproducible manner.
Here, we introduce Cuore, an integrated platform that enables the culturing and electrical stimulation of 3D engineered muscle tissues, specifically designed to measure contractile force and kinetics in a multi-well format. This system is compatible with primary, immortalized, and induced pluripotent stem cell (iPSC)-derived cell lines, allowing for the creation of patient-specific models of neuromuscular diseases. Cuore also supports customizable stimulation protocols to explore muscle maturation, exercise patterns, and fatigue behaviour—parameters that are directly relevant to the function of dystrophic muscle. Cuore utilizes optical interferometry-based detection to provide accurate and highly precise measurements of contraction, with micro-Newton force sensitivity and millisecond temporal resolution [a]. The accompanying software automatically extracts key metrics of contractility, and the platform is compatible with imaging-based readouts as well as downstream biochemical assays. We here present example datasets generated using both skeletal and cardiac muscle models.
In summary, Cuore offers a powerful functional assay for studying muscle pathophysiology and evaluating therapeutic interventions in vitro. By delivering high-fidelity contractility measurements in human-relevant tissue models, it has the potential to accelerate preclinical drug development and enhance decision-making in neuromuscular disease research.
[a] A. Iuliano et.al., Adv. Mater. Technol. 2023, 8, 2300845. https://doi.org/10.1002/admt.202300845