ISS/Collaborative Research: Studying the Effects of Microgravity on 3D Cardiac Organoid Cultures

Exposure to microgravity during spaceflight is known to lead to cardiac atrophy, which is a reduction in tissue mass of the heart that causes debilitating changes in heart function. Cardiac atrophy can also present itself in patients suffering from cancer and other diseases, including muscular dystrophies, diabetes, sepsis and heart failure. Because cardiac atrophy is not well understood, this project seeks to improve fundamental understanding of cell and tissue function during progression of cardiac atrophy. Undertaking this research is an interdisciplinary and multi-institutional team comprised of biomedical engineers and scientists with complementary expertise in cardiac tissue bioprinting and cellular and molecular biology. Using the micro-gravity environment of the International Space Station (ISS) to induce atrophy, the team will use bioprinted heart tissue to study changes in tissue function. The knowledge gained will support an improved understanding of how and why cardiac atrophy occurs, which may lead to improved treatment strategies. The project will also develop a workshop for K12 students around tissue engineering on the international space station as well as implement a seminar for medical students, interns, and residents about the benefits and challenges of transitioning research from an Earth-based laboratory into space. Two objectives have been established for this project. First, to compare and contrast the morphology, viability, and altered energy metabolism in 3D bioprinted cardiac organoids under microgravity and Earth's gravity. Second, to study the epigenetic changes in 3D bioprinted cardiac organoids under microgravity and assess how these changes may affect the development of cardiac atrophy when compared to Earth's gravity. Specifically, the team will engineer and validate a chip design for culturing of cardiomyocytes, fibroblasts and endothelial cells to investigate underlying biological and signaling mediators responsible for damage to cells during microgravity exposure, leading to possible cardiac atrophy. Findings may suggest that epigenetic events could be one of the mechanistic bases for microgravity‐induced gene expression changes related to cardiac atrophy and may facilitate the development of countermeasures to prevent the adverse effects of microgravity or other atrophy-inducing pathologies. 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.