Space Tissue Loss - Stem Cell Regeneration (STL-Regeneration) - 07.14.16
Space Tissue Loss - Stem Cell Regeneration (STL-Regeneration) is a Department of Defense Space Test Program payload studying stem cell regeneration in mouse cell culture in microgravity examining the effects of tissue regeneration in space. Cell culture in microgravity serves as a model system for understanding necrosis of tissue following severe injuries on Earth. Science Results for Everyone
Information Pending Experiment Details
Eduardo A. C Almeida, Ph.D., Moffett Field, CA, United States
Ruth K. Globus, Ph.D., Ames Research Center, Moffett Field, CA, United States
Walter Reed Army Institute of Research, Silver Spring, MD, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
National Laboratory - Department of Defense (NL-DoD)
ISS Expedition Duration
March 2010 - September 2010
The STL experiment model has not previously flown in the CCM, although the hardware has flown on several previous Space Shuttle mission.
- The Space Tissue Loss - Stem Cell Regeneration (STL-Regeneration) investigation examines the effects of space flight on the biology of mouse stem cell differentiation.
- The STL-Regeneration experiment determines the space flight affects on the cellular biology of differentiation,gene expression patterns, and modifications to DNA sequences that regulate genes that control cell differentiation.
The Space Tissue Loss - Stem Cell Regeneration (STL-Regeneration) studies how cells develop into specialized tissue types, or "differentiate" in space. The experiment will use mouse embryoid bodies, which are ball-shaped collections of mouse embryonic stem cells, to study the effects of microgravity on the cells' ability to differentiate.
On Earth, the mouse embryoid body is considered a model to study how the cells and tissue of a whole organism differentiate and develop. Because mouse embryonic stem cells can differentiate into any type of adult tissue found in the body, scientists are using them to investigate the ways cells grow and regenerate to better understand the cellular, biochemical, and genetic processes of healing wounds and tissue development in space.
STL-Regeneration plans to identify common conserved cellular and molecular space flight response mechanisms in cells relevant to normal cellular function and disease progression by profiling expression levels of Sm proteins and changes in cellular differentiation, immune function, and stress response before and after pathogenic bacteria infection of tissue culture cells.
The Cell Culture Module (CCM) hardware used in STL investigation is designed specifically to study the effects of microgravity on cell culture. For this experiment, off-the-shelf hollow fiber bioreactors are used as basic cell support structures. The CCM allows controlled physiologic maintenance, manipulation, and testing of the cells. The CCM is a completely automated, temperature controlled system designed to help scientists study the effects of microgravity on cells in space. The study includes cultured tissue test materials in continuous flow modules.
Exposure to microgravity causes cells to react in a destructive cascade similar to wounds. This breakdown of tissue and function presents serious challenges to the health of humans in space. Astronauts traveling to the moon or Mars in microgravity may experience injury or, initiating the wound healing process. Astronauts exposed to pathogens in space may also experience reduced immune function and susceptibility to infection. The experiment results could help determine new and improved wound healing treatment for astronauts as well as provide further insight into bacteria/host interactions in space.
Cellular and bacterial microgravity experiments are used to research methods of treating Earth-bound injuries and infection where cellular degeneration and decreased immune response can occur in traumatic wounds and unused limbs. The application spans both military and civilian injuries and immune response on Earth.
Operational Requirements and Protocols
The STL investigations are self contained and require crew interaction for activation, status checks, and reentry. Rails will contain cell lines treated with different agents. Following return to Earth, the rails will be returned to the respective investigator for in-depth analysis.
Decadal Survey Recommendations
Information Pending^ back to top
On earth, organisms are constantly under the influence of gravity which seems to be essential for normal cell growth and tissue function. This “mechanical loading” (resistance against a force), from living on the Earth’s surface, stimulates and promotes tissue regeneration by stem cells. In contrast, being weightless in space appears to cause tissue degeneration, including the inhibition of regenerative stem cell development. Because of this, it is important to understand how removing gravity’s load on stem cells may impact tissue regenerative health. Scientists found that exposure to microgravity for 15 days inhibits mouse embryonic stem cells (mESCs) differentiation. Three dimensional spherical stem cell aggregates, also known as embryoid bodies or EBs, grown in space appeared to consume slightly less nutrients (glucose) than those grown back on Earth, indicating reduced cell number, mass, or reduced metabolic rate. Additionally, space-flown stem cell retained their self-renewal (making more stem cells) markers, suggesting that Earth’s gravity is required for normal replication and differentiation of mESCs. Finally, stem cells recovered from space and then cultured back on the ground showed greater stemness (the ability to self-renew and become different cell types), changing more readily, for instance, into specialized cardiac muscle cell colonies. These results show that mechanical unloading of stem cells inhibits their differentiation and preserves stemness, and possibly provide a cellular explanation for decreased tissue regeneration in space and in disuse conditions on earth.^ back to top
Blaber EA, Finkelstein H, Dvorochkin N, Sato K, Yousuf R, Burns BP, Globus RK, Almeida EA. Microgravity reduces the differentiation and regenerative potential of embryonic stem cells. Stem Cells and Development. 2015 November 10; 24(22): 2605-2621. DOI: 10.1089/scd.2015.0218.
Ground Based Results Publications
Landis WJ, Hodgens KJ, Block D, Toma CD, Gerstenfeld LC. Spaceflight Effects on cultured embryonic chick bone cells. Journal of Bone and Mineral Research. 2000; 15(6): 99-112. PMID: 10841178.
Reece JS, Miller MJ, Arnold MA, Waterhouse C, Delaplaine T, Cohn L, Cannon TF. Continuous Oxygen Monitoring of Mammalian Cell Growth on Space Shuttle Mission STS-93 with a Novel Radioluminescent Oxygen. Applied and Environmental Microbiology. 2003; 104(1): 1-11.
Ikenaga M, Hirayama J, Kato T, Kitao H, Han Z, Ishizaki K, Nishizawa K, Suzuki F, Cannon TF, Fukui K, Shimazu T, Kamigaichi S, Ishioka N, Matsumiya H. Effect of Space Flight on the Frequency of Micronuclei and Expression of Stress-Responsive Proteins in Cultured Mammalian Cells. Journal of Radiation Research. 2002; 43: S141-S147. DOI: 10.1269/jrr.43.S141. PMID: 12793748.
Harris SA, Zhang M, Kidder L, Evans GL, Spelsberg TC, Turner RT. Effects of Orbital Spaceflight on Human Osteoblastic Cell Physiology and Gene Expression. Bone. 2000; 26(4): 325-331. PMID: 10719274.