Personalising medicine with advanced organ-on-a-chip models
While rare diseases can cause chronic health problems or even be life-threatening, many lack effective treatment. This is in part due to a lack of physiologically relevant disease models. “This lack of relevant models results in high failure rates of therapeutics in clinical testing, which in turn constrains the number of new drugs reaching patients,” says Georges Dubourg, a researcher at the BioSense Institute. With the support of the EU-funded CISTEM project, Dubourg led an effort to help close this research gap. Specifically, the project, which received support from the Marie Skłodowska-Curie Actions programme, developed an organ-on-a-chip (OoC) based disease model for cardiomyopathy associated with Duchenne muscular dystrophy, one of the most severe forms of inherited muscular dystrophies. OoC is a type of artificial organ that uses microfluidic technology to create a tailored, dynamic and 3D microenvironment inspired by organ-level functions in vivo.
A patient-specific heart-on-a-chip model
In the CISTEM project, researchers merged the latest advancements in induced pluripotent stem cell technology with microfluidic, microsystem and sensor technologies. “The result is a patient-specific, heart-on-a-chip model,” notes Dubourg. While the model is innovative in and of itself, it is comprised of many innovative components, each of which could prove invaluable to developing additional OoC models. For example, the model includes a microfluidic station capable of controlling the flow of fluid inside the device. This in turn enables accurate flow and pressure control with a stable diffusion gradient, allowing the model to better mimic the physiological configuration of the actual organ. The CISTEM model also includes two breakthrough platforms for performing electrical measurements through an endothelial barrier. “These systems have a huge potential for assessing a drug’s effect on the cardiac system and endothelial barrier,” adds Dubourg. Another key component is tailored 3D multicellular cardiac microtissues that could be used for personalised medicine and treatment.
Potential to increase the success rate of new drugs
Both the heart-on-a-chip solution developed during the project and the OoC models it is likely to inspire are set to have a multifaceted impact on healthcare research. “These models have the potential to significantly increase the success rate of new drugs and provide new treatments for currently untreatable rare diseases,” explains Dubourg. “Furthermore, the use of advanced models that can better predict a drug’s effect will decrease the high cost of developing new drugs and, ultimately, the cost of the drug once it reaches the market.” Dubourg also notes that OoC models can considerably reduce the number of animals used in biomedical research.
Advancing towards market readiness
Of course, there is still a long way to go to getting OoC models to the level needed to reap these many potential benefits. For example, the technology readiness level of the different platforms and models must be further developed and fully tested. However, thanks to the technology and expertise developed during the CISTEM project, Dubourg is confident that OoC models will continue to advance towards market readiness. “Not only did this project lay the foundation for new research initiatives, results and products, it also trained the next generation of OoC researchers dedicated to thinking outside the laboratory scale and seeing that these game-changing models have a positive impact on patient care,” concludes Dubourg.
Keywords
CISTEM, medicine, organ-on-a-chip, rare diseases, health, disease models, artificial organ, stem cell, healthcare research
