Effects of Microgravity on Stem Cell-Derived Heart Cells (Heart Cells) - 07.12.17

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Spaceflight causes a suite of negative health effects, which become more problematic as crew members stay in orbit for long periods of time. Effects of Microgravity on Stem Cell-Derived Cardiomyocytes (Heart Cells) studies the human heart, specifically how heart muscle tissue, contracts, grows and changes (gene expression) in microgravity and how those changes vary between subjects. Understanding how heart muscle cells, or cardiomyocytes, change in space improves efforts for studying disease, screening drugs and conducting cell replacement therapy for future space missions.
Science Results for Everyone
Information Pending

The following content was provided by Joseph C. Wu, M.D., Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Heart Cells

Principal Investigator(s)
Joseph C. Wu, M.D., Ph.D., Stanford University School of Medicine, Stanford, CA, United States

Co-Investigator(s)/Collaborator(s)
Peter H. Lee, M.D., M.P.H., M.S., The Ohio State University, Columbus, OH, United States
Arun Sharma, Stanford University School of Medicine, Stanford, CA, United States

Developer(s)
BioServe Space Technologies, University of Colorado, Boulder, CO, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits, Scientific Discovery

ISS Expedition Duration
September 2015 - March 2016; March 2016 - September 2016

Expeditions Assigned
45/46,47/48

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • The goals of the Effects of Microgravity on Stem Cell-Derived Heart Cells (Heart Cells) investigation involve increasing the understanding of the effects of microgravity on heart function, the improvement of heart disease modeling capabilities, and the development of appropriate methods for cell therapy for people with heart disease on Earth. 
  • It is hoped that this investigation provides knowledge that may impact disease modeling, drug discovery, and Heart cell therapy.

Description

With extended stays aboard the International Space Station (ISS) becoming commonplace and as NASA prepares for exploration class space missions beyond low earth orbit, the need to better understand and mitigate the negative effects of spaceflight on various bodily and cellular functions is becoming increasingly important. Specifically, there is great interest in the effects of microgravity on the human heart, with a particular emphasis on understanding the microgravity effects on cardiomyocyte physiology and gene expression. The goal of the Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery (Heart Cells) investigation is to look further into the effects.
 
Primary human heart tissues, which would be useful for in vitro microgravity studies on heart function, are very difficult to obtain and maintain in culture. Likewise, the characteristics of animal cells are sufficiently different from their human counterparts that their use is limited. Instead, this investigation aims to use heart cells derived from human induced pluripotent stem cells (hiPSCs), which have emerged as a novel tool for drug discovery and cell therapy in cardiovascular medicine, to study the effects of microgravity on cardiac function and gene expression.
 
Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes (CM) derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. The use of hiPSC-CMs to explore and model the cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable, and are used as a model to investigate the effects of microgravity on cardiac function. First, hiPSCs are produced from a racially diverse group of volunteers by obtaining their skin samples through a routine skin biopsy, and then these terminally-differentiated cells are reverted to a pluripotent stem cell state using commercially available reprogramming vectors. The hiPSC-CMs are then mass produced using a high-efficiency hiPSC differentiation protocol that has been fine-tuned in the laboratory.
 
In collaboration with BioServe Space Technologies, which is well-versed in the maintenance of cell culture experiments in spaceflight, the hiPSC-CMs are cultured on the ISS for up to a month. One group of cells is treated in-flight and stored at 4°C for post-flight ground-based analysis of gene expression using RNA-sequencing. Another group of cells is to remain under standard culture conditions and recovered post-flight for further analysis in the laboratory, including examining the cells’ morphology, function, structural integrity, and maturity level. This study represents the first time that hiPSC technology is used to study the effects of microgravity on human heart cells.

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Applications

Space Applications
Extended stays aboard the International Space Station (ISS) are becoming more common, and future crews will stay in space for even longer periods as they travel to the moon, asteroids or Mars. Living without gravity’s influence for long periods can cause negative health effects such as muscle atrophy, including potential atrophy of heart muscle. This investigation uses human skin cells that are induced to become stem cells, which can differentiate into any type of cell. The researchers then force them to grow into human heart cells, and culture them on the ISS for one month. Results demonstrate how heart muscle cells (cardiomyocytes) change on a cellular and molecular level in space, improving understanding of microgravity’s negative effects.

Earth Applications
Stem cells can become any type of cell in the body, which makes them a valuable research tool. In this investigation, researchers use human skin cells and convert them into induced pluripotent stem cells (hiPSCs). These cells are then used to study cardiac muscle. Understanding changes to heart muscle cells benefits cardiovascular research on Earth, where heart disease is a leading cause of death in many countries.

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Operations

Operational Requirements and Protocols

Three (3) subjects and 3 replicates for each condition is required, for a total of 18 samples. Media exchanges occur at predetermined time points. Imaging of the heart cell tissue occurs 3-5 days following a media exchange. All media exchanges occur within 10 days of previous exchange. Active cells must return to Earth within 10 days of last media exchange. Cells must be maintained at 37°C, with 5% CO2 for all active phases of the experiment including transport to/from ISS. One of the three 6-well plates is preserved with RNAlater and conditioned and stowed to 4°C, and returned to Earth at 4°C.

Three 6-well BioCells each in its own BioCell Habitat are launched at 37°C via SpaceX Dragon to ISS. On ISS the BioCell Habitats are incubated inside SABL with 5% CO2 for up to 28 days. At predetermined days, media exchanges, preservation or imaging of the cells is completed under as sterile conditions as possible. Fluid exchanges occur within the Microgravity Sciences Glovebox. BioServe’s inverted microscope is used for video imaging. Cold stowage is used for 37°C transport to, and from, ISS for the active 6-well plates. One plate is preserved on board ISS, stowed at 4°C, and returned to Earth at 4°C.
 

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Decadal Survey Recommendations

Information Pending

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Results/More Information

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Imagery