Stemnovate is working on an exciting project with the European Space Agency. We are working with multinational collaborators using our cells to help create a 3D musculoskeletal model to investigate the effects of microgravity on the musculoskeletal system and test and develop therapeutics to prevent bone and muscle wasting. This work can help improve astronaut health and allow for more extended space missions. Moreover, such studies can help understand osteoporosis and the ageing process.

 

This project is fascinating because human cells generated in the laboratory can be part of space missions and open new avenues for research. Although the sound of space-travelling bone and muscle cells may sound unlikely or the work of science fiction, this research is by no means the first of its kind. Scientists have been doing all kinds of experiments in space as the low gravity gives a unique environment that is difficult to replicate on Earth. Thousands of experiments have been conducted in space, from growing lettuce to searching for dark matter. (1)

           

Cell culture research in space helps us understand some of the fundamental processes in cells and how they depend on gravity. By monitoring how the activity and gene expression in cells are affected by gravity, we can begin to understand the processes that rely on mechanotransduction –cells converting mechanical stimuli into a chemical response. This research is also crucial for understanding microgravity's effects on astronauts' health, from the cellular level to whole organ systems. Changes on a system level are more evident with bone and muscle wasting and changes in blood pressure and heart rate. (2) Cell changes are inevitable, with microgravity disrupting the mechanotransduction in cells. Understanding how these changes to our cells affect human health is crucial.

Studies have shown that microgravity and even extended bed rest – like low gravity, reduces the mechanical load and the movement of cells in our body- reduces immune response. The Thymus, which generates most of our T-cells, is impaired by microgravity and creates less of our immune cells. Our T-cells are not able to grow, and the cells we do have can become dysfunctional, significantly reducing our ability to fight infection. This change in the immune system can even cause latent viral infections (such as asymptomatic herpes viruses, which approximately 70–95% of the population have) to reactivate, with astronauts experiencing cold sores due to the reactivation of latent HSV-1. Studies also show a reduction in the number and activity of natural killer (NK) cells, which are vital for the immune system as they can destroy infected or cancerous cells. Microgravity makes these cells less able to attack targets by reducing their cytotoxicity and ability to recognise target cells. With less effective NK cells, this reduction in immune response may increase the cancer risk associated with space travel due to space radiation. (3) (4)

Microgravity also has some interesting effects on Stem cells. Without gravity, the fluids in cells cannot circulate, and many pathways and signals interrupt stem cells' ability to differentiate into other cells. At normal gravity, clusters of stem cells form Embryoid bodies, but in microgravity, clusters do not fully differentiate into multiple cell types. Instead, they continue to express genes indicating self-renewal associated with 'stemness' and do not show the standard markers expected from fully differentiated cells. This inhibition in differentiation means stem cells are less able to replace and regenerate tissue. (5) This is especially noticeable in the skin as microgravity conditions cause thinning and for any wounds to heal much slower. Astronauts frequently complain of dry or cracked hands and have a higher tendency for skin infections. (6) 

Although stem cells retaining their stemness and being less able to differentiate will likely be a problem in the body, this can benefit when growing stem cells in culture. The retention of stemness means stem cells in culture can grow more quickly, making cell culture faster. Under regular gravity, cells are pulled together and compressed, hindering their growth outwards. Production of iPSCs in space would be fine. The reduced tension between cells would help growth faster than under normal gravity, allowing the quick mass production of iPSCs, which could then be sent back to Earth for possible use as personalised therapeutics. (7) Another application of microgravity in biomanufacturing is bioprinting, a technique used to create artificial tissue by printing 3D constructs with bioinks made from live cells and biomaterials, such as collagen. Without gravity-induced densification, complex shapes are possible using less viscous bio-inks, allowing for more advanced tissue manufacture. (6)

We are excited to be part of a collaboration project with the European Space Agency and contribute to the research happening in space. We also started working with collaborators in France with expertise in scaffolds that can help better bone differentiation and create niches for these cells to obtain densities for modelling and studying osteoporosis. This project opened new horizons as we look for out of the box solutions for problems affecting our lives on Earth.

Works Cited

1. Astronauts have conducted nearly 3,000 science experiments aboard the ISS. Witze, Alexandra. 2020, Nature.

2. Bioastronautics: The Influence of Microgravity on Astronaut Health. Blaber, Elizabeth, Marçal, Helder and Burns, Brendan P. 5, 2010, Astrobiology, Vol. 10.

3. Natural killer cells after altaïr mission. I.V. Konstantinova, M. Rykova, D. Meshkov, C. Peres, D. Husson, D.A. Schmitt. 8-12, 1995, Acta Astronautica, Vol. 36, pp. 713-718. 0094-5765.

4. How does spaceflight affect the acquired immune system? Akiyama, T., Horie, K., Hinoi, E. et al. 14, 2020, npj Microgravity, Vol. 6.

5. Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic Stem Cells. Elizabeth A. Blaber, Hayley Finkelstein, Natalya Dvorochkin, Kevin Y. Sato, Rukhsana Yousuf, Brendan P. Burns, Ruth K. Globus, and Eduardo A.C. Almeida. 22, Nov 2015, Stem Cells and Development, Vol. 24, pp. 2605-2621.

6. Wound and Skin Healing in Space: The 3D Bioprinting Perspective. Cubo-Mateo, N. and Gelinsky, M. 2021, Frontiers in bioengineering and biotechnology, Vol. 9.

7. Cedars-Sinai. Leveraging Space to Advance Stem Cell Science and Medicine. Cedars-Sinai. [Online] Dec 2021. https://www.cedars-sinai.org/newsroom/leveraging-space-to-advance-stem-cell-science-and-medicine/.