Space Tissue Loss - Stem Cell Regeneration (STL-Regeneration) - 08.03.16

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
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
This is heavy. Gravity seems essential to normal tissue health, with the forces it generates stimulating and promoting regeneration by stem cells. NASA experiments in microgravity on ISS show sharply reduced ability by mouse embryonic stem cell cultures to develop and generate different tissue types. Embryo-like aggregates of stem cells cultured in space retained many gene expression markers of early development, but failed to express most of the genes characteristic of normal tissue differentiation such as in muscle, bone and the immune system. Most stem cells flown in microgravity could still self-renew and become different cell types upon return to Earth’s gravity. In sharp contrast, stem cell self-renewal is rapidly lost on earth as normal differentiation proceeds. This is new evidence that gravity mechanical stimulation on Earth promotes stem cell-based tissue regeneration, and that mechanical unloading in microgravity, as well as disuse on Earth, can slow-down normal tissue regeneration. This research, conducted by Scientists from the Space Biology Program at NASA Ames Research Center, presents new findings that are important for both regenerative medicine and space exploration.

The following content was provided by Eduardo A. C Almeida, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom:

Principal Investigator(s)
Eduardo A. C Almeida, Ph.D., Moffett Field, CA, United States

Co-Investigator(s)/Collaborator(s)
Ruth K. Globus, Ph.D., Ames Research Center, Moffett Field, CA, United States

Developer(s)
Walter Reed Army Institute of Research, Silver Spring, MD, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory - Department of Defense (NL-DoD)

Research Benefits
Information Pending

ISS Expedition Duration
March 2010 - September 2010

Expeditions Assigned
23/24

Previous Missions
The STL experiment model has not previously flown in the CCM, although the hardware has flown on several previous Space Shuttle mission.

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Experiment Description

Research Overview

  • 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.

Description
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.

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Applications

Space Applications
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.

Earth Applications
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.

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Operations

Operational Requirements and Protocols

Four rails with individual flow paths and biocreactors will be housed inside the CCM hardware. Two rails will be used for each investigator. The configuration will allow for redundancy in experiments, increasing the probability of successful tests and samples returning to Earth for analysis.


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.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

On Earth, organisms are constantly under the influence of gravity that shapes normal cell growth and tissue function. This “gravity mechanical loading” (resistance against forces generated by the acceleration of bodies by gravity), stimulates and promotes normal tissue repair and regeneration by stem cells. A prime example of this phenomenon is the effect of exercise, such as lifting weights against gravity, which promotes new bone and muscle formation as well as enhanced immunity. Many tissue-regenerative processes are mediated by reservoirs of adult stem cells, in this case in the bone marrow, that proliferate and differentiate to form new bone and increase the number of immune cells in circulation. In contrast, disuse on Earth, or being weightless in space, causes tissue degeneration, both by active degradation of existing tissue, as well as an inhibition of stem cell-based tissue regeneration. Because of this, Space Biology scientists at NASA Ames Research Center are seeking to understand how removing gravity’s load on stem cells in microgravity may impact the molecular mechanisms regulating their contribution to tissue regenerative health. To conduct their studies, scientists used a laboratory “embryoid body” model (EB) of stem cell-based tissue regeneration and exposed them to microgravity on ISS for 15 days, either preserving them in space or returning them live to Earth for further studies. In this model, mouse embryonic stem cells are first cultured in adherent monolayers with a growth factor (Leukemia Inhibitory Factor or LIF) that maintains their immortality. When adhesion and LIF are removed, the cells form embryo-like spheroids that proceed to terminally differentiate into many non-dividing cells and tissue types, recapitulating in the laboratory, the process of forming or regenerating new tissue such as muscle, bone, and blood among others. The patterns of gene expression during the transition between stem cells and differentiated tissues, in microgravity versus on Earth at 1g, was then studied, revealing that specific genes markers of new tissue formation and regeneration are not expressed normally in microgravity. In fact, the large majority of tissue-specific genes that appeared on earth at 1g, failed to reach the same expression levels in microgravity. In sharp contrast, many genes required for stem cell self-renewal and immortality were overexpressed in microgravity, suggesting that gravity is required for inducing the transition between stem cell progenitors and differentiated cells involved in tissue regenerative health. Finally, stem cells recovered from EBs flown in space and then cultured back on Earth showed greater “stemness” (the ability to self-renew and generate any cell type), changing more readily upon induction, for instance, into specialized cardiac muscle cell colonies. These results show that mechanical unloading of stem cells in microgravity inhibits their differentiation and preserves their stemness, possibly providing a cellular mechanistic explanation for decreased tissue regeneration in space and in disuse conditions on Earth. The next steps in these NASA studies are to understand the molecular sensing and switching mechanisms that allow stem cells to detect gravity loading and respond by initiating the process of cell proliferation and differentiation leading to tissue regeneration.

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Results Publications

    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.

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Ground Based Results Publications

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ISS Patents

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Related 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.

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Related Websites

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Imagery