At a Glance
- Results from an ISS National Lab investigation led by researchers at the Stanford University School of Medicine were published in the journal Stem Cell Reports.
- This investigation was the first to use human induced pluripotent stem cell-derived cardiomyocytes to examine cardiac cell function in microgravity.
- Results demonstrated that microgravity alters cardiac function at the cellular level, mirroring changes seen in the hearts of some astronauts during spaceflight.
- Insight gained from this investigation could help lead to improved cardiovascular disease modeling and drug screening for populations on Earth.
Today, the journal Stem Cell Reports published results from a research team at Stanford University School of Medicine that utilized the International Space Station (ISS) U.S. National Laboratory to examine cardiac cell function in microgravity. Knowledge gained from this research contributes to a better understanding of the mechanisms behind cardiac function—which could enable improved cardiovascular disease modeling and drug screening and aid in the development of future cell replacement therapies.
The research team, led by Principal Investigator Dr. Joseph Wu and Co-Investigator Dr. Arun Sharma, examined microgravity’s effects on the functional properties and gene expression of cardiomyocytes (specialized cardiac muscle cells) derived from human induced pluripotent stem cells (iPSC). Results from the investigation, which launched on SpaceX’s ninth commercial resupply services mission, demonstrated that microgravity alters cardiac function at the cellular level—and these changes mirror changes seen in the whole heart during spaceflight.
Findings from this research could benefit not only astronauts on future long-duration spaceflight missions but also patients with cardiovascular disease back on the ground. According to the U.S. Centers for Disease Control and Prevention (CDC), more than 600,000 Americans die from heart disease each year—accounting for one out of every four deaths in the U.S.
Looking at a Cellular Level
It is well known that spaceflight affects cardiac function and that long-term exposure to microgravity leads to cardiac deconditioning. Previous studies of cardiac function in microgravity have been conducted either at the tissue, organ, or systemic level or using rodent cardiomyocyte models, which do not exactly replicate all the interactions of human cardiac muscle cells.
To better understand how microgravity influences human cardiac function on a cellular level, Dr. Wu and his team used live human iPSC-derived cardiomyocytes from three individuals. To develop the samples, peripheral blood mononuclear cells from the individuals were reprogrammed on the ground into stem cells that were then differentiated into cardiomyocytes. The team then cultured the human iPSC-derived cardiomyocytes onboard the ISS National Lab for 5.5 weeks and examined the cells’ structure, function, and gene expression.
Evaluating Microgravity-Induced Changes
Once the samples were returned to Earth, the research team evaluated the cells for changes in morphology and structure and found no clear differences between the flight and ground control samples. However, the team found that microgravity did induce functional changes in the cells, and these changes remained after the cells were return to normal gravity. As part of the functional analysis, the team assessed calcium-handling, which plays a key role in cardiac contractile function, and found that the spaceflight cells displayed indications of decreased calcium recycling and beating irregularity.
The team also conducted RNA-sequencing analysis on the samples both during spaceflight and after return to Earth and found changes in the level of gene expression among several genes. Spaceflight cardiomyocytes were harvested at 4.5 weeks for in-orbit analysis and then again 10 days postflight for analysis back on the ground. Among the in-orbit, postflight, and ground control samples, 2,635 genes were differentially expressed, including genes involved in mitochondrial metabolism.
The numbers of differentially expressed genes between the ground and in-orbit samples and between the postflight and in-orbit samples were much greater than the number of differentially expressed genes between the postflight and ground samples. These findings suggest that the gene expression pattern of human iPSC-derived cardiomyocytes changes during spaceflight and then reverts to a pattern more similar to ground controls after return to normal gravity.
Understanding Cardiomyocyte Function
This investigation represents the first time human iPSC-derived cardiomyocytes were used to model microgravity’s effects on human cardiomyocyte structure and function. Results demonstrate that microgravity-induced changes in human cardiac function occur not just at the whole-heart level but also at the cellular level.
Insight gained from this research could provide a better understanding of cardiomyocyte function, leading to improved cardiovascular disease modeling and drug screening. This investigation also helped lay the foundation for future studies of cardiac function in microgravity using tissue chip systems and three-dimensional organoids.