Abstract

Modeling the Effects of Spaceflight on the Human Heart Using Stem Cell-derived Cardiomyocytes

Arun Sharma, Research Fellow, Harvard Medical School

With extended stays aboard the International Space Station (ISS) becoming commonplace as humanity prepares for exploration-class space missions, the need to better understand the effects of microgravity on cardiac function during spaceflight is critical. However, primary human heart tissues, which would be useful for in vitro studies on heart function, are difficult to obtain and maintain. As a model system, we utilized cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) to study the effects of microgravity on human cardiac function and gene expression at the cellular level. We derived hiPSCs from three healthy volunteers and produced hiPSC-CMs using a high-efficiency differentiation protocol. We cultured hiPSC-CMs in a microgravity environment aboard the ISS for approximately one month, during which weekly media changes were conducted. We analyzed the gene expression, structure, and function of space-flown and groundside control hiPSC-CM samples using RNA-sequencing, immunofluorescence, calcium imaging, and contractility assessment. This study represents the first time that hiPSC technology has been used to study the effects of spaceflight on human cardiomyocyte function and demonstrates that microgravity affects human cardiomyocyte function on the cellular level.