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

Alexa Wnorowski; Arun Sharma; Haodong Chen; Haodi Wu; Ning-Yi Shao; Nazish Sayed; Chun Liu; Stefanie Countryman; Louis S. Stodieck; Kathleen H. Rubins; Sean M. Wu; Peter H.U. Lee; Joseph C. Wu

Stem Cell Reports (Dec 2019)

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

Alexa Wnorowski,
Arun Sharma,
Haodong Chen,
Haodi Wu,
Ning-Yi Shao,
Nazish Sayed,
Chun Liu,
Stefanie Countryman,
Louis S. Stodieck,
Kathleen H. Rubins,
Sean M. Wu,
Peter H.U. Lee,
Joseph C. Wu

Affiliations

Alexa Wnorowski: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University Schools of Medicine and Engineering, Stanford, CA 94305, USA
Arun Sharma: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Haodong Chen: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Haodi Wu: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Ning-Yi Shao: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Nazish Sayed: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Chun Liu: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Stefanie Countryman: BioServe Space Technologies, Department of Aerospace Engineering Sciences, University of Colorado, Boulder, CO 80309, USA
Louis S. Stodieck: BioServe Space Technologies, Department of Aerospace Engineering Sciences, University of Colorado, Boulder, CO 80309, USA
Kathleen H. Rubins: Astronaut Office, NASA Johnson Space Center, Houston, TX 77058, USA
Sean M. Wu: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA
Peter H.U. Lee: Department of Surgery, The Ohio State University, Columbus, OH 43210, USA; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA
Joseph C. Wu: Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding author

Journal volume & issue: Vol. 13, no. 6
pp. 960 – 969

Abstract

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Summary: 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. : 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. Keywords: cardiomyocytes, cardiology, induced pluripotent stem cells, microgravity, spaceflight, heart, stem cell, calcium imaging, modeling, metabolism

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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