Human heart cells are changed by spaceflight but return to mostly normal on Earth, according to a study that examined how the human heart functions in spaceflight. The scientists were surprised as to how quickly human heart muscle cells could adapt to the environment in which they are placed.
The research team examined the cell-level cardiac function and gene expression in human heart cells that were cultured aboard the International Space Station (ISS) for 5.5 weeks. They found that heart muscle cells -- derived from stem cells -- adapted well to their environment during and after spaceflight.
The analysis, says the team, shows that exposure to microgravity altered the expression of thousands of genes, but largely normal patterns of gene expression reappeared within 10 days after returning to Earth.
These findings provide insight into how the human heart functions at the cellular level in spaceflight. This study suggests that the human heart muscle cells are very adaptable to the environment in which they are placed, including microgravity. Microgravity is an environment that is not very well understood in terms of its overall effect on the human body, and studies like this will be able to help shed light on how the cells of the body behave in space," Dr. Joseph C. Wu, Director, Stanford Cardiovascular Institute at Stanford University School of Medicine, told MEA WorldWide (MEAWW).
The researchers explain that human heart muscle cells, like the whole heart, change their functional properties in spaceflight and compensate for the apparent loss of gravity by changing their gene expression patterns at the cellular level.
"This study does not tell us how the heart as a whole changes in microgravity. There are several other types of cells in the heart that were not included in this study. We also do not know how the cells might react if they were exposed to microgravity for a longer period of time. However, these are both things we can test in the future. The results we observed in this study will allow us to focus those future studies on characteristics of the heart muscle cells we know are strongly affected by microgravity," Dr. Wu told MEAWW.
With extended stays aboard the ISS becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function, say experts. Past studies have shown that spaceflight induces physiological changes in cardiac function. Astronauts on space shuttle missions have experienced reduced heart rate, lowered arterial pressure, and increased cardiac output. But to date, most cardiovascular microgravity physiology studies have been conducted either in non-human models or at tissue, organ, or systemic levels, says the team.
"The National Aeronautics and Space Administration [NASA] Twin Study demonstrated that long-term exposure to microgravity reduces mean arterial pressure and increases cardiac output. However, little is known about the role of microgravity in influencing human cardiac function at the cellular level," says the study published in 'Stem Cell Reports'.
Accordingly, the research team used human induced pluripotent stem cells to study the effects of spaceflight on human heart function.
"We studied human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We generated hiPSC lines from three individuals by reprogramming blood cells and then differentiated them into hiPSC-CMs," says the study.
Dr. Wu explains that human induced pluripotent stem cells (hiPSCs) are stem cells that can be produced from a small sample of blood or skin through a process called "reprogamming".
"These hiPSCs can be then turned into almost any cell type of interest, including beating human heart muscle cells, or cardiomyocytes. Since these hiPSC-derived cardiomyocytes mimic the function of true adult human heart cells, we can use them as a model for how the cells of the human heart respond to microgravity," Dr. Wu told MEAWW.
Beating hiPSC-CMs were launched to the International Space Station aboard a SpaceX spacecraft, as part of a commercial resupply service mission. Simultaneously, ground control hiPSC-CMs were cultured on Earth for comparison.
"Upon return to Earth, space-flown hiPSC-CMs showed normal structure and morphology. However, they did adapt by modifying their beating patterns and calcium recycling patterns," the findings state.
The researchers performed RNA sequencing. "These results showed that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples. A comparison of the samples revealed that hiPSC-CMs adopt a unique gene expression pattern during spaceflight, which reverts to one that is similar to groundside controls upon return to normal gravity," says the study.
The findings, according to the researchers, could provide insight into cellular mechanisms that could benefit astronaut health during long-duration spaceflight, or potentially lay the foundation for new insights into improving heart health on Earth.
"We know that humans can spend months and years in space. Through decades of analyses, we know that the human heart as a whole organ changes its shape, size, and function in spaceflight. These changes are one reason why astronauts must exercise in space for hours every day to keep their heart muscles strong. While our cell-based experiments were able to confirm that changes also occur on the cellular level, we cannot directly translate this to the organ-level without further studies. The changes in our hiPSC-cardiomyocytes are not adverse effects, but rather adaptations to microgravity. The changes reflect how the cells of the human body can quickly adapt to a low gravity environment," Dr. Wu told MEAWW.
The research team now plans to test different treatments on the human heart cells to determine if they can prevent some of the changes the heart cells undergo during spaceflight.
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