3D Printed Muscle Tissues for Drug Discovery With Mantarray™ Platform by Curi Bio
Curi Bio, a developer of human stem cell-based platforms for drug discovery, announced the commercial launch of the Mantarray™ platform for human-relevant 3D heart and skeletal engineered muscle tissue contractility analysis. Curi’s Mantarray platform can serve for the discovery of new therapeutics by providing parallel analysis of 3D EMTs with adult human-like functional profiles of healthy and disease models.
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It goes without saying that when the drug is developed, it needs to be tested on a highly relevant model before being approved for the clinical trials. Do we have such highly relevant models for all diseases? Obviously, no. But there are some advances which bring us closer to literally “crafting” such models by ourselves -- 3D tissue printing.
Along with other 3D models, such as organoids and organ-on-chip systems, 3D printed tissues have multiple advantages compared to the flat 2D cell cultures. To mention briefly, organoids are 3D multicellular tissue constructs, which are grown from the stem cells, being one of the most widely used 3D models for high-throughput drug discovery. Even though organoids partially resemble the organ, they usually lack some essential components (like vascularization, immune system elements etc.), making them not a fully representative model. On top of that, organoids usually suffer from heterogeneity, so even though it is cheaper and easier to use organoids compared to more advanced 3D-tissue models, the drawbacks should be considered.
On the other hand, 3D-printed tissues and organ-on-chip are more controlled systems, where the last one can represent even the inter-organ connections, which are “compressed” into a microfluidic chip. This level of control over organ-on-chip also means that this model stands further from how the organs would be built physiologically and brings some engineering challenges. In comparison, 3D-printed tissues don’t provide such a full picture, but at the same time it can be an optimally controlled model for discovering novel therapeutics.
Why can 3D-printing of tissues be better than organoids raised from stem cells, despite a higher cost and technically more complicated process? To name a few reasons, when tissues are 3D-printed, they are first modeled on a computer, meaning that the researcher can create the design which benefits the research best (like to build in the vascularization, for example). Also, 3D tissue printing can assist in mimicking some specific disease conditions, as well as to create the models which would be more complicated to grow as organoids, including the contractive muscle tissues.
According to Curi Bio, for cardiac and skeletal muscle diseases direct assessment of contractile output constitutes the most reliable metric to assess overall tissue function, as other ‘proxy’ measurements are poor predictors of muscle strength. 3D engineered muscle tissues derived from human induced pluripotent stem cells (iPSCs) offer a promising route to model the contractile deficiencies seen in the heart and muscles of patients.
Curi suggested a possible solution for the preclinical drug testing on cardiac and skeletal muscle models with their Mantarray platform, which is according to the company an easy-to-use, scalable, and flexible biosystem. The Mantarray platform leverages a proprietary, label-free, electromagnetic measurement system for parallel contractility assessment of up to 24 engineered muscle tissues simultaneously. It can also utilize a variety of contractile cell types.
The system has built-in electrical stimulation capabilities, enabling users to create individual stimulation protocols for each well, for both short and long-term pacing of cardiac and skeletal muscle models. Additionally, Curi developed consumable Mantarray plates that are specifically designed for cardiac and skeletal muscle applications.
Curi offers Mantarray technology for applications in drug discovery, disease modeling, and safety and efficacy screening. The models of human diseases can be created and tested on the Mantarray platform using human iPSC-derived cells or patient-derived myoblasts from healthy or affected individuals. For example, Mantarray 3D engineered muscle tissues can be formed from cells harboring disease-causing mutations (patient-derived or gene-edited; iPSC-derived or primary) to model human diseases such as Duchenne muscular dystrophy, myotonic dystrophy type 1, hypertrophic and dilated cardiomyopathies, and more.
Magnetic detection of drug-induced contractile changes is one of the methods developed by Curi Bio for drug safety and efficacy screening. Acute drug responses can be measured within a comparatively short time span to detect dose-response-like behavior. Alternatively, Curi also mentioned that chronic experiments can be performed over the course of days to weeks for longer-term studies.
Multiple companies are driven by the opportunities of 3D tissue printing, developing both the technical equipment with materials and the pipelines for tissue bioprinting itself, followed by its further validation for drug testing. Organovo Holdings develops a range of 3D tissue models for medical research and therapeutic applications. They own a 3D Bioprinting platform, which they already used to create the models for healthy liver, kidney, intestine, skin, bone, skeletal muscle and more. Organovo has a separate platform for high-throughput 3D models, unlike Curi Bio, who stated that their Mantarray platform is theoretically compatible with 96-well and 384-well plates, but it is still to be validated.
At the same time, a Finland-based company BRINTER provides a solution for bioprinting organs and tissues, including tumor tissue models. According to the company, their 3D printing platform ensures the physiologically relevant and reproducible results, and some of their publications highlight the efforts in bioprinting vasculature and patient-specific tumors. On the other hand, Aspect Biosystems, a biotech start-up combining microfluidics and 3D bioprinting, develops bioprinted tissue therapeutics. They bioprint pancreatic and liver tissues, which then could be surgically implanted into the body, representing another significant application for 3D tissue bioprinting.
