Valentina Fossati Explains Why We Sent Patient Cells to SpaceNews
Cover photo: Dr. Valentina Fossati (NYSCF) and Jason Stein (Aspen Neuroscience) prepare cells for launch. Photo credit: Space Tango
Why send cells affected by multiple sclerosis (MS) and Parkinson’s disease to the International Space Station (ISS)? Hear NYSCF Senior Research Investigator Valentina Fossati, PhD, tell the story of her pioneering experiment – conducted in collaboration with the National Stem Cell Foundation and Space Tango – to understand the drivers of neurodegeneration by studying patient cells in microgravity. This talk was delivered as part of the 2020 ISS R&D Conference. Watch the video or read the transcript below.
Today I’d like to tell you a story about stem cells, neurodegenerative disease, and how biological research is reaching new heights – quite literally.
My journey with stem cells started nearly 20 years ago. I was an undergraduate biotechnology student, and a brand-new field had just exploded called ‘regenerative medicine,’ the foundation of which is stem cells.
As a young scientist dedicated to finding cures for major diseases, I was captivated by stem cells, as they are the superheroes of the cellular universe. They are the only cells in the human body with the ability to turn into more than 200 types of cells, including those that make up the heart, brain, liver, eye, and more. Stem cells also have the power to regenerate indefinitely: they could fill up an entire room in just a few days. Stem cells are uniquely powerful because they allow us to do 3 things we have never been able to do before:
First, by studying the stem cells of patients, we can see how the cells become damaged and cause disease.
Second, we are able to test the safety and efficacy of drugs on those diseased patient cells.
And third, we are learning how to replace the cells affected by a disease with a patient’s own healthy cells.
In 2008, when I was a postdoctoral researcher, my symptoms started to appear. A couple of months of exams led to the words I was most afraid to hear: you have multiple sclerosis. I started to look at the literature surrounding my disease. What I found was puzzling. Almost every study focused on the immune system, as MS is considered an autoimmune disease. But we did not have a model for looking at the human brain cells in a dish, to investigate how the cells within the brain could contribute to the disease process. I decided that if I was going to stay a scientist, I was going to study MS, I was going to do it with stem cells, and I was going to find out what was happening in the brain.
Now, my lab does just this. We use stem cells from patients with MS and other neurodegenerative diseases to generate the different cells of the brain and study what causes them to die. There is one specific type of brain cell that I find especially intriguing, and that’s microglia. Microglia are the brain’s immune cells. They constantly patrol the brain, and when they find that something is off, they spring into action by causing inflammation and engulfing debris or pathogens.
Normally, this process is good – it’s a defense mechanism that keeps your brain healthy. But, in neurodegenerative diseases like MS or Parkinson’s, we think that microglia go a little crazy, and their exaggerated response can make them toxic to neurons.
To explore the interplay between these cells, my lab began creating organoids – 3D clusters of human tissue made from stem cells – that recapitulate the brain’s environment.
With our tiny organoids, we can see how the brain’s different cell types interact and why microglia may be acting out.
My work is funded in part by the National Stem Cell Foundation, and in 2018, they reached out to me about an exciting idea: what if we were to send organoids to the ISS?
Now, you may be wondering, why would we send organoids to the ISS? When microglia become activated, they completely change their shape and their motility. And based on previous experiments, we believe that microgravity can interfere with the ability of immune cells to do this. So, microgravity serves as a unique circumstance in which to tease apart these healthy and diseased behaviors, pointing us toward new treatment targets.
This work is also important because we have more and more people going to space for longer and longer times, and we need to understand the impact of microgravity on our cells. We already have astronauts spending up to a year in space, and studies have shown that astronauts can display altered gene expression in their immune cells as a result of time spent in microgravity. And just think about if we ever send people to Mars. That’s a one-way trip, and we need to know how microgravity affects our cells in the long term.
So, we teamed up with a company called Space Tango that specializes in space flight technology, and they made this absolutely incredible tool called the CubeLab. The CubeLab is a lot like how it sounds – it’s a shoebox-sized, self-sustainable machine that functions as a miniature laboratory. Since it is fully automated, it allowed us to carry out our analyses from Earth and ensure that the astronauts on ISS didn’t have to become stem cell biologists to keep our experiments running.
Before the CubeLab and its inhabitants made their journey up to ISS, we had to prepare everything here on Earth. We generated brain cells from the stem cells of MS and Parkinson’s patients using our state-of-the-art automation technologies at the NYSCF Research Institute in New York, and then the cells had to make the arduous journey to Cape Canaveral in Florida for launch. I say arduous because this trip, along with the entire preparation process, isn’t as easy as it seems. Cells have to live in very particular conditions, and it was really critical that all the pieces come together at the exact times that they needed to. Rocket launches, as you know, are intricately planned and timed. If something goes wrong in cell preparation, you could miss the launch entirely.
We had our share of setbacks – our cells got temporarily lost in transit, for example – but everything came together when it needed to.
Our first launch, in August of 2019, served as a test run of the equipment, ensuring that everything could function in the experiment. The launch was delayed because of weather conditions, so I was actually in my taxi to the airport watching the livestream on my phone when I saw the rocket disappear into the sky. It was stunning and emotional, and I started to cry right there in the car. I think I scared the driver, but I couldn’t help it. It was breathtaking.
For our second launch, in December, I returned to Cape Canaveral hoping to witness it in-person. We were delayed once again, but on the second day the rocket was able to go. I’m glad I was there to see my work take to the sky firsthand. What I remember most vividly was the sound. You can feel the sonic boom in your body.
After 30 days aboard ISS, the cells made their way back to Earth, and we are studying their gene expression, structure, and secretions to tease apart sickness behaviors. We are also continuously optimizing experimental protocols for future launches to improve the way we, and other labs, conduct stem cell research in space.
As a bit of an aside, I knew that one of the astronauts on ISS was Italian, and this made myself, and my postdoc Davide, who is also Italian, very excited. It was a bit of a moment of national pride for us to know that even though we were working from very different places, we all had this shared heritage. We even scrambled to send him a little video message, and we got a picture with him handling the CubeLab – it was such an honor!
Another exciting aspect of this experiment was how it engaged the public. As a stem cell biologist, my work isn’t often high-profile. I spend my days in my lab, and we publish our findings, but never before has one of my projects drawn so much interest from scientists and non-scientists alike. It is so encouraging to know that people are as excited about this new frontier for research as I am, and I am hopeful that by combining the skills of the many talented people in this collaboration, we will make many insightful discoveries about MS and Parkinson’s.
It’s incredible to know now, when I look up at the sky, that my own little piece of science had its place among the stars, and that one day, this work could be leveraged to help the patients I care about so deeply. Thank you for listening, and thank you to all the people involved in this journey.
Read more about this project here.