FREEDOM AND SAFETY
Understanding how and why the human body declines with age - and how to slow or prevent it - is an extremely important area of research, especially as the older population continues to grow.
In addition to providing significant public health benefits, preventing age-related disease could have significant economic impacts on society. For example, a 10 percent reduction in sarcopenia - the degenerative loss of skeletal muscle mass - would save 1.1 billion in healthcare costs annually.
However, aging is difficult to study, as it require decades and decades of follow-up research.
Microgravity offers a solution, as it can serve as a model for accelerated aging. Physiological changes occur approximately 10 times faster in microgravity and it contributes to loss of muscle and bone mass, cardiovascular degeneration, immune deficiency and optic nerve swelling.
“A lot of the physiologic changes that occur within the human body in microgravity are similar to what occurs in the human body during the aging process,” explained Siobhan Malany, PhD, the Director of Translational Biology at Sanford Burnham Prebys Medical Discovery Institute. “One of the main ideas is looking at degeneration in microgravity at a more accelerated rate and using that to model the real-time progress in a way you just can’t do on Earth because of the time frame.”
Malany is the founder of Sanford Burnham Prebys’ first spin-off company, micro-gRx, which is studying the effects of microgravity on human muscle myocytes on the ISS. They are working in partnership with Israeli company SpacePharma, and received a grant from Space Florida as part of its Florida-Israel Innovation Partnership program. They also received funding from CASIS.
To study the impact of microgravity - and potentially aging - on muscles in space, Malany’s team collected skeletal muscle cells from different aged donors, as well as donors with different physical exercise statuses, from Florida Hospital.
The samples were isolated from biopsies, grown and enriched into muscle myotubes and then placed in a gel that mimics extracellular matrix cells in the body.
Eventually, the samples will be incorporated into a Lab-on-Chip system designed specifically for use in space, which is slotted to go up to ISS on SpaceX CRS-15 this summer.
“The question we are trying to answer is - are the cells that are isolated from young, athletic donors going to change significantly in microgravity to mimic more of the older cells after a few weeks in terms of their gene expression? We are sending both types of cells, and in a way they will be a control for each other as it is difficult to have a control on Earth as you can’t control for the flight.”
The Lab-on-Chip system is designed to be a completely closed, automated system that can be remotely controlled from Earth. The system features two chips - one for the older phenotype cells and one for the younger - with three chambers on each chip, for replication purposes. There is a microscope in the system that allows Malany and her team to look at the muscle cells as they are growing and differentiating in the system aboard the ISS in real-time.
“It’s a culturing lab, so for any type of cells it’s all the same principal,” explained Malany. “It has inlets and outlets to put in culture media, to add in reagents, to preserve cells, to really do an end-to-end experiment if we needed to. There are a lot of different things that you can do.”
The Lab-on-Chip includes a multiplexed pump system, with two types of operating pumps built for the ISS that have remote control capabilities. The entire system is packaged into what’s called a ‘CubeSat’ design - integrated for flight in partnership with Space Tango - which contains a fluid handling system, optical sensors, electronics assembly, chip mount, and operational software. This provides environmental control, daily monitoring of data and analytics, power on accent, accurate flow rates in range of 10-500 microliters/min, non-pulsating, positive displacement pumping, bubble-free operation, and built in temperature control (heating and cooling) for pump and reservoir.
Creating Lab-on-Chip technology that can operate completely autonomously in space is a challenge, said Malany.
“We are almost trying to advance the technology at the same as we are trying to have relevant biology,” she said.
Once aboard the ISS, the experiment will last 14 to 21 days. At that time, a fixative that preserves the cells will be added to keep cells in a cold state. The Lab-on-Chip technology is expected to be returned to Malany and her team within 30 to 45 days after the launch.
Once the Lab-on-Chip is back in Malany’s lab, her team will perform RNA extraction, transcriptomics analysis and do a comparative gene analysis between the two different aged cell phenotypes and between the samples sent to the ISS and the ones kept on ground.
While much will be learned from the experiment’s first trip to ISS, future trips will be required to understand the full picture, said Malany.
“The concept is exciting, but it is challenging,” she said. “There are a lot of hurdles, but I think eventually we will have multiple flights and repeat experiments and technology will be more and more advanced.”
She expects that this area of research will continue to expand and grow within the life science field.
“Now you’ve got prominent institutions on board, and more and more people interested in sending stem cells and primary cells and other organ-on-a-chip systems to the ISS,” said Malany. “If you are looking at the number of people that are attending conferences and presenting and the number of technology groups that are collaborating with researchers to send things to the space station, it is just growing incredibly.”