Q&A: Space

Healio Interviews

Healio Interviews

With the rise of commercial spaceflight and astronauts’ stays aboard the International Space Station becoming longer, researchers seek to understand the impact of microgravity in low-Earth orbit on the function of the heart.

Arun Sharma, PhD, assistant professor of biomedical sciences and research scientist at the Smidt Heart Institute, Regenerative Medicine Institute and Cedars-Sinai Cancer at Cedars-Sinai, and colleagues at Stanford University collaborated with researchers on the International Space Station National Laboratory to do just that.

With their experiment overseen by NASA astronaut Kate Rubins, PhD, the researchers used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity in low-Earth orbit on measures of cardiac function and gene expression.

The hiPSC-CMs were sent to the space station aboard a SpaceX Dragon transport during a commercial resupply service mission and cultured for 5.5 weeks.

Sharma and colleagues observed that microgravity exposure was associated with increased hiPSC-CM Ca2+ transient decay tau indicative of decreased calcium recycling rate that persisted after return to normal gravity conditions, according to findings published in Stem Cell Reports.

In addition, RNA analyses showed that 2,635 genes — including those associated with mitochondrial metabolism — were differentially expressed while in microgravity; however, the gene expression signatures returned to normal upon return to normal gravity.

At the International Space Station Research and Development Conference in July, Sharma will host a fireside chat alongside Stefanie Countryman, director of BioServe Space Technologies, the company that designed stem cell culture dishes used for this study, to discuss the future of CV research in space.

Sharma spoke with Healio about this research, collaboration with colleagues aboard the space station, and what these findings indicate for the CV health of both individuals in space as well as lessons learned about hearts here on Earth.

Healio: Why did you choose to pursue this particular area of CV research?

Sharma: We decided to pursue this area of research to get a better understanding of how the human heart is impacted, at the cellular level, by spaceflight. We have an understanding of what happens to the heart at the organ level, from decades of astronaut studies, but we have much less of an understanding of what happens to the individual cells of the human heart. This is why we wanted to use pluripotent stem cell-derived cardiomyocytes (heart muscle cells) as our cellular model of human heart tissue.

Healio: Can you provide some background on how spaceflight affects heart function?

Sharma: The heart is a muscle, and like the other muscles of the body, it changes shape and size during extended exposure to microgravity and during spaceflight. The heart and the other muscles of the body lose some of their mass, undergoing what’s called atrophy. The heart also changes its shape to become more spherical as opposed to its normal fist-shape.

Healio: What was the design and goal of your research culturing induced pluripotent stem cells on the International Space Station?

Sharma: The goal of our study was to understand what happens to human heart cells at the cellular level during spaceflight. Thus, we took advantage of hiPSCs, which allow us to mass produce human heart cells from just a few drops of blood. We “reprogram” those blood cells to hiPSCs in a process that takes a month to complete, and then once the hiPSCs are made, they can be turned into beating human heart cells within a few weeks.

In terms of study design, we produced these hiPSC-derived heart cells and then sent a sample of those cells to the space station, where they would be examined for spaceflight-induced changes in beating ability, shape/size and gene expression. We also grew a “parallel” set of hiPSC-derived heart cells in our laboratory on Earth to serve as a comparison for this experiment.

Healio: What did you learn?

Sharma: We found that human heart cells rapidly adapt to the microgravity environment by changing their beating ability and gene expression. These changes can occur within days of the cells being placed in orbit.

Healio: How can these data be applied to ensure CV health among those partaking in spaceflight?

Sharma: We may be able to use this data in a fundamental way to understand how the human heart functions in space, and perhaps in the future, we could use these cells to develop countermeasures to keep the hearts and muscles of astronauts healthy and strong during extended periods of spaceflight.

Healio: Do these results have any implications for improving the CV health of those here on Earth?

Sharma: The changes that happen to the human body in space can resemble a form of “accelerated aging,” whereby muscles, bones and tissues degrade and change at a faster rate than normal.

Thus, our studies could be used to better understand cardiac diseases on Earth, where heart cells become unhealthy due to environmental or genetic factors.

Healio: Did you face any unique challenges or hurdles utilizing and/or communicating with the cell culture facilities aboard the space station?

Sharma: The space station is an exceptionally unique research environment, and the capabilities aboard the International Space Station are quite impressive. There are advanced microscopes and cell growth stations that are comparable to what are available in our biomedical laboratories on Earth.

There are technical challenges in how we grow cells in space, which requires unique engineering solutions. To grow our heart cells in space in microgravity, we collaborated with biomedical engineers at BioServe Space Technologies, who designed custom cell culture dishes for extended cell growth aboard the space station.

Healio: What can you tell us about your upcoming fireside chat at the 12th annual International Space Station Research and Development Conference?

Sharma: I am looking forward to discussing this experiment and future planned CV experiments with Stefanie Countryman, director of BioServe Space Technologies, and Donna Roberts, MD, of the International Space Station National Laboratory. It will be great to both look back and look ahead at the next phase of CV research in space.

Healio: What further research is planned and/or needed to better understand the CV impact of spaceflight?

Sharma: Future studies will use new model systems, such as 3D heart-on-a-chip constructs and 3D cardiac organoid structures, to get a better understanding of how the human heart functions in space. Since the heart is a 3D organ, these next-generation 3D model systems will help take our studies to the next level.

Healio: Anything else you would like to add?

Sharma: Our laboratory is also actively involved in other NASA studies examining stem cell production and biomanufacturing in space. More on that here: https://www.cedarssinai.org/newsroom/mission-ax-2-set-to-launch-stem-cells-to-space/

Arun Sharma, PhD, can be reached at [email protected].