GOALI: ISS Engineered Heart Tissue Chip to Assess Nanomedicine Strategies in a Spaceflight Model of Cardiac Aging

Heart disease accounts for one in every five deaths in the United States, with age being a major contributing factor. Intriguingly, the unique environmental conditions of spaceflight, such as microgravity and exposure to galactic cosmic radiation, have been associated with cardiovascular deterioration in astronauts similar to that found in older individuals.

In fact, cardiac arrhythmias (erratic heartbeats) have been noted in astronauts aboard the International Space Station with no prior history of abnormal heartbeats. Thus, spaceflight has been proposed to model cardiovascular aging. Previous studies found that a direct determinant of spaceflight-induced heart dysfunction is an increase in highly reactive chemicals known as reactive oxygen species (ROS) caused by exposure to radiation and microgravity.

High levels of ROS target the mitochondria and nuclei in cells throughout the body inducing cellular dysfunction and DNA damage – hallmarks of spaceflight and age-induced heart disease. This research team aims to investigate if nanoparticles designed to scavenge ROS can prevent dysfunction in mitochondria, thereby protecting against spaceflight-induced cardiac abnormalities.

In this project, the research team will deploy an engineered heart tissue chip in both space and Earth-bound experiments to test the therapeutic effects of nanoparticles in functioning heart tissues. If such a therapy is found to be efficacious in improving cardiac function during spaceflight, it may be used to treat age-related heart disease among the general population.

This is the first project to test nanomedicines in space. This project also incorporates the training of young scientists and students and provides the opportunity to gain first-hand experience in bioengineering research.

This project aims to determine if reactive oxygen species (ROS)-scavenging nanoparticles can prevent spaceflight-induced mitochondrial dysfunction, thus protecting against spaceflight-induced cardiomyopathies. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) will be generated on Earth and matured into physiologically relevant, functional 3D engineered heart tissues (EHTs).

ROS-scavenging nanoparticles with surface targeting motifs for both mitochondria and the nucleus will be synthesized and optimized to treat the EHTs. Ground-based experiments using x-ray radiation and a simulated-microgravity random positioning machine platform will aid in optimizing conditions and protocols for the spaceflight experiment. Aboard the International Space Station (ISS), EHTs will be maintained for one month, during which time they will be treated with the ROS-scavenging nanoparticles.

Real-time force measurements will be available during spaceflight to provide continuous functional assessment of the EHTs' condition with complete analyses to be conducted post-flight in the laboratory. The experimental outcomes include contractile function, DNA damage, mitochondrial health, total cellular ROS, and calcium handling. This project will advance our understanding of the role of ROS in spaceflight-induced cardiovascular dysfunction and the potential of ROS-scavenging nanoparticles as a countermeasure.

Moreover, these results will provide a basis for developing effective countermeasures against cardiovascular dysfunction in both astronauts and the Earth-bound aging population. (Project integration and operation on the ISS will be provided by the Center for the Advancement of Science in Space’s implementation partner, BioServe).

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.