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

doi:10.1016/j.stemcr.2019.10.006

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

Stem Cell Reports. 2019 Dec 10;13(6):960-969. doi: 10.1016/j.stemcr.2019.10.006. Epub 2019 Nov 7.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ BioServe Space Technologies, Department of Aerospace Engineering Sciences, University of Colorado, Boulder, CO 80309, USA.
⁵ Astronaut Office, NASA Johnson Space Center, Houston, TX 77058, USA.
⁶ 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.
⁷ Department of Surgery, The Ohio State University, Columbus, OH 43210, USA; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
⁸ 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. Electronic address: joewu@stanford.edu.

Abstract

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biomarkers
Calcium / metabolism
Cell Culture Techniques
Cell Differentiation
Cells, Cultured
Computational Biology / methods
Energy Metabolism
Fluorescent Antibody Technique
Gene Expression Profiling
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism*
Molecular Sequence Annotation
Myocytes, Cardiac / cytology*
Myocytes, Cardiac / metabolism*
Space Flight*
Weightlessness*

Substances

Biomarkers
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding