Prof. Sonja Schrepfer | in front of the Golden Gate Bridge in San Francisco. After winning a 750,000 US dollar NASA grant, her team relocated to California for one year for the project 'Heart in Space' at the University of California San Francisco (UCSF).
AcademiaNet: Prof. Schrepfer, you're studying how smooth muscle cells behave in zero gravity with a NASA grant. What did you find out from your cell experiments in San Francisco?
Prof. Sonja Schrepfer: We just started the experiments last January and the studies are still ongoing. However, we already have many exciting data on smooth muscle cell (SMC) behavior at zero gravity. For these studies, we are using a rotator designed by NASA, in which cells can be cultured in simulated microgravity. Our current data suggest that single smooth muscle cells respond to microgravity on the miRNA, RNA and protein level: microRNAs, RNA and proteins are changing and are similar to patients with cardiovascular diseases. The SMC phenotype switches from the differentiated to the un-differentiated type, enabeling the SMCs to proliferate.
However, it seems as if the vascular wall tension protects the cells from these changes. We are currently investigating this phenomen in vitro and in vivo using various techniques - RNA sequencing, microRNA Arrays, PCRs, immunoblots, etc - and expect the first validated results by the end of the year.
You also sent mice to space to live aboard the ISS for a month. What are the results from your space mice?
To study microgravity in the lab on earth, we are using simulated microgravity in vitro and in vivo. However, these studies have their limitations. Therefore, we are also investigating the cardiovascular health of mice in space. We received tissue from two missions, RR1 and RR3, and we are scheduled for our own mission - hopefully for next year.
The samples from the twenty mice so far, ten mice from each mission, are currently investigated in our lab. The main challenge in the beginning was that tissues have never been dissected or analysed from microgravity animals before; RR1 means rodent research 1 and was the first rodent mission.
We needed to modify and establish our protocols for our assays. We were lucky, and the tissue quality was good, and we were able to start our assays which are still ongoing. RR1 and RR3 had different mouse strains and therefore we can validate our data and demonstrate that the results are not strain specific. We are very happy to be part of this exciting research and so far our hypothesis described from our in vitro studies seems to be confirmed in vivo.
You and your team have already discovered a molecule that could prevent this kind of vascular stenosis. What can you tell us about it?
We identified a small molecule, named DCA, which is a PDK2 inhibitor: effective in inhibiting vascular stenosis. The study was published in Nature in 2014. We just received the patent rights from Stanford and are planning clinical trials. This molecule prevents hyperpolarisation of mitochondria in SMCs, one of the key players in SMC de-differentation and proliferation, which was first demonstrated by our group.
The molecule is easy to take, it can be mixed with drinking water, and didn't show any side effects in the dosages needed to prevent vascular stenosis. Therefore, we are investigating if DCA might be useful for astronauts on long-term missions in deeper space. In this regard, researchers from the National Aeronautics and Space Administration NASA published recently in Nature Scientific Reports that astronauts in deeper space show a significant higher risk of cardiovascular disease and the mortality was significant higher compared to astronauts on earth.
This study demonstrates the importance and relevance of our research understanding vascular health in space. There is an urgent need to provide a preventive therapy for astronauts in the future. We hope that our data will make a significant contribution to understand the underlying mechanism and to develop a therapeutic/preventive strategy for long-term spaceflights.
Usually you study stem cells in the cardiovascular system – how did you get the idea to study 'Heart in Space'? And how did you find out about the NASA grant?
Our lab is investigating the immunobiology of pluripotent stem cells and their potency for the cardiovascular system as well as identifying novel mechanisms related to cardiovascular disease. In this regard, we identified a novel pathway, called PDK2, involved in the development of vascular stenosis as described above.
When my husband, the cardiac surgeon Prof. Tobias Deuse, and I joined the Scientific Meeting of the American Heart Association in 2013 to present our data on DCA, we also visited the NASA Johnson Space Center before catching our flight back to Germany. The exhibition was excellent and supported by presentations about NASA's research and the planned Mars mission and its challenges for human beings. At the end of the presentation, we received a paper with the weblink to NASA's research website.
During the flight back, we discussed potential cardiovascular risk factors in microgravity. Being back in Germany, I visited the website and realised an upcoming deadline for which our idea fitted very well. A few months later, we received the amazing news that our grant was funded and that we would be able to investigate vascular health in space. We were thrilled and the whole lab as well as our collaborators were very excited to be part of this amazing opportunity.
Dear Prof. Schrepfer, thank you very much for this interesting interview!
Interview: Susanne Dambeck