Abstract 379: Effects of Microgravity on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

Abstract

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 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 hiPSC-CM 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 flight, post-flight, and ground control hiPSC-CM samples using RNA-sequencing, immunofluorescence, calcium imaging, and contractility assessment. Exposure to microgravity on the ISS resulted in decreased contractile velocity and calcium recycling in the hiPSC-CM, along with increased beating irregularities. RNA-sequencing analysis demonstrated that there were 2635 genes differentially expressed with p≤0.05 between flight, post-flight, and ground control samples. These included genes involved in metabolism, DNA/RNA modification, and molecular transport, indicating that these pathways may be permanently altered by long-term space flight . This study represents the first time that hiPSC technology has been used to study the effects of microgravity on human cardiac function and is the first to demonstrate that microgravity affects human heart function on the cellular level.