Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

• Published in: Stem cell reports Vol. 13; no. 6; pp. 960 - 969
• Main Authors: Wnorowski, Alexa, Sharma, Arun, Chen, Haodong, Wu, Haodi, Shao, Ning-Yi, Sayed, Nazish, Liu, Chun, Countryman, Stefanie, Stodieck, Louis S., Rubins, Kathleen H., Wu, Sean M., Lee, Peter H.U., Wu, Joseph C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.12.2019; Elsevier
• Subjects: calcium imaging; cardiology; cardiomyocytes; heart; induced pluripotent stem cells; metabolism; microgravity; modeling; spaceflight; stem cell; cardiomyocytes; microgravity; spaceflight; modeling; stem cell; induced pluripotent stem cells; metabolism; calcium imaging; cardiology; heart
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2019.10.006

With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function. [Display omitted] •Microgravity exposure resulted in changes in hiPSC-CM calcium-handling properties•2,635 genes were differentially expressed among flight, post-flight, and ground•Pathways related to mitochondrial function were enriched in space-flown hiPSC-CMs In this article, Wu and colleagues demonstrate that human cardiomyocytes, like the whole heart, change their contractile properties in microgravity and compensate for the apparent loss of gravity by altering their gene-expression patterns. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function at the cellular level.