Mantarray 3D Engineered Muscle Tissue Platform Demonstrates Clinically-Relevant Disease Stratification of an in vitro DMD Model


Translational Research

Poster Number: 312


Shawn Luttrell, PhD, Curi Bio, Daniel Lih, MS, Curi Bio, Kevin Gray, Curi Bio, Samir Kharoufeh, Curi Bio, Bonnie Berry, PhD, Curi Bio, Christal Worthen, PhD, Curi Bio, Greg Luerman, PhD, Curi Bio, Nicholas Geisse, PhD, Curi Bio

Accurately modeling healthy and disease conditions in vitro is vital for the development of new treatment strategies and therapeutics. For cardiac and skeletal muscle diseases, direct assessment of contractile output is a reliable metric to study overall tissue function, as other ‘proxy’ measurements are poor predictors of muscle strength. Human 3D engineered muscle tissues (EMTs) from induced pluripotent stem cell and primary cell sources hold great potential for modeling contractile function. However, the bioengineering strategies required to generate these predictive models presents limitations for many investigators. Here, we have developed a platform and device that utilizes 3D EMTs in conjunction with a label-free magnetic sensing array (Mantarray). The platform enables facile and reproducible fabrication of 3D EMTs using virtually any cell source and is coupled with highly parallel direct measurement of contractility. This approach enables clinically relevant functional measurements of muscle, stratification of healthy and diseased muscle phenotypes, and facilitates therapeutic modality-agnostic, dose-dependent compound safety and efficacy screening. Here we present a 3D model of Duchenne muscular dystrophy that utilizes skeletal muscle EMTs formed from an isogenic pair of healthy and diseased cells. These tissues achieve robust twitch and tetanic responses upon stimulation. The model presents functional deficits across numerous metrics of contractility, including force and fatigability. EMTs remain functional for several weeks in culture and provide a large experimental window to not only study therapeutic effect, but also disease phenotypes that may present at later stages of development and maturity. These data demonstrate a first-and-only commercial platform integrating individual, well-based control of electrical stimulation across a 24-well plate to pace 3D tissues, modeling exercise regimens or damage protocols in muscle constructs. Stimulation is coupled with automated assessment of 3D skeletal and cardiac muscle contraction, providing an inclusive, high throughput platform for disease modeling and therapeutic discovery.