Space Tissue Loss - The Effects Microgravity on Stem Cell-Based Tissue Regeneration: Keratinocyte Differentiation in Wound Healing (STL-Regeneration-Keratinocytes) - 07.29.14
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Space Tissue Loss - The Effects of Microgravity on Stem Cell-Based Tissue Regeneration: Keratinocyte Differentiation in Wound Healing (STL-Regeneration-Keratinocytes) is a Department of Defense (DoD) Space Test Program payload flying both NASA and DoD science that uses cell and tissue cultures in microgravity to study the effects of tissue regeneration and wound healing in space.
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Telemedicine and Advanced Technology Research Center, Ft. Detrick, MD, United States
United States Department of Defense Space Test Program, Johnson Space Center, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
National Laboratory - Department of Defense (NL-DoD)
ISS Expedition Duration
March 2011 - September 2011
Previous ISS Missions
Versions of STL experiments and CCM have flown on the following Shuttle missions: STS-45, STS-53, STS-56, STS-59 (two units), STS-63, STS-66, STS-69, STS-70, STS-72, STS-77, STS-78, STS-80, STS-86, STS-93 (two units), STS-95, STS-118 and STS-131.
- Space flight, both in low Earth orbit and in deep space, has many physiological consequences for life, including a large array of conditions such as bone loss, muscle loss, loss of cardiovascular capacity, possible defects in wound and bone fracture healing, and impaired immune function.
- One common feature of the effects of space flight is that affected tissues rely on tissue-specific stem cells for regeneration and repair. Because of this, effects on stem cell health in these tissues are likely a key component of the physiological response to microgravity, and have the potential to explain multiple degenerative conditions.
- This study focuses on the effect the space environment has on the growth and health of regenerative tissues within the epidermis and epidermal keratinocytes (tissues that make up the outer layer of the skin). This focus on keratinocytes allows investigation of a specific important space flight concern in wound healing while allowing for finely-tuned research on the mechanisms of how cell cycles are started and stopped.
Space Tissue Loss - The Effects of Microgravity on Stem Cell-Based Tissue Regeneration: Keratinocyte Differentiation in Wound Healing (STL-Regeneration-Keratinocytes) space flight environment affect the cellular, biochemical, and genetic processes of stem cell differentiation (becoming specialized) into epidermal keratinocytes, and to start understanding the cellular and molecular basis for wound healing defects reported in microgravity. For STL-Regeneration-Keratinocytes, mouse embryonic stem (mES) cells are grown in hollow fiber bioreactors and incubated in the Cell Culture Module (CCM). The CCM provides a temperature controlled environment (37ºC), medium perfusion, and medium circulation. Cells are returned to Earth either fixed in RNALater 2, which preserves messenger ribonucleic acid (mRNA)and deoxyribonucleic acid (DNA), or alive. Once back on Earth, some of the cells are fixed in paraformaldehyde for cell biology studies, and other cells may be incubated further for migration and wound healing assays. Biochemical, physiological, and genetic analyses are conducted to characterize how the cells differentiated in microgravity. Also, studies are conducted to determine if epigenetic (changes in gene function that do not involve changes in DNA sequence) processes of differentiation have been affected. The data from the space flight specimens is compared to the data from specimens that are grown in a ground control CCM. By conducting a comparative analysis, the PI is able to identify space flight specific effects on cell differentiation.
The Cell Culture Module (CCM) hardware used in Space Tissue Loss - The Effects of Microgravity on Stem Cell-Based Tissue Regeneration: Keratinocyte Differentiation in Wound Healing (STL-Regeneration-Keratinocytes) 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 STL payload is made up of three experiments that are conducted inside the CCM, including STL-Regeneration-Keratinocytes. 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. Crewmembers traveling in microgravity may experience injury or illness, initiating the wound healing process. Crewmembers 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.
Cellular microgravity experiments are used to research methods of treating Earth-bound injuries where cellular degeneration and decreased immune response can occur in traumatic wounds and unused limbs. The application spans across both military and civilian injuries and immune response on Earth.
Housed inside the CCM are 4 rails (or mounting apparatus) that hold bioreactors for cell culture with individual flow paths. Two rails with 12 bioreactors are used for the NASA investigator and 2 rails with 12 bioreactors are shared between the DoD investigators. The configuration allows for redundancy in experiments, increasing the probability of successful tests and samples returning to Earth for analysis.
STL-Regeneration-Keratinocytes is self contained and requires crew interaction for activation, status checks, and re-entry. Rails contain cell lines treated with different agents. Following return to Earth, the rails are returned to the investigator for in-depth analysis.
Ground Based Results Publications
Chromiak JA, Shansky J, Perrone C, Vandenburgh HH. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids. In Vitro Cellular and Developmental Biology - Animal. 1998; 34(9): 694-703.
Davis TA, Wiesmann WP, Kidwell W, Cannon TF, Kerns L, Serke C, Delaplaine T, Pranger A, Lee KP. Effect of spaceflight on human stem cell hematopoiesis: suppression of erythropoiesis and myelopoiesis. Journal of Leukocyte Biology. 1996; 60(1): 69-76. PMID: 8699125.
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.
Lewis FC, Goodwin TJ, Linnehan RM, Wolf D, Hire K, Hammond TG, Hammond TG, Campbell W, Benes E, O'Reilly K, Globus RK, Kaysen JH. Gene Expression in Space. Nature Medicine. 1995; 5(4): 359.
Doty SB, Stiner D, Telford WG. The Effect of Spaceflight on Cartilage Cell Cycle and Differentiation. Journal of Gravitational Physiology. 1999; 6(1): P89-P90.
Landis WJ. An Overview of Vertebrate Mineralization with Emphasis on Collagen-Mineral Interaction. Gravitational and Space Biology. 1998; 12(1): 4.
Gerstenfeld LC, Landis WJ. Gene Expression and Formation of Extracellular Matrix in a Primary Osteoblast Culture System. Gravitational and Space Biology. 1993; 7(1): 30.
Space Biosciences Division
Walter Reed: Combat Casualty Care
NASA Image - S118E10350 - Seen in this image is the hardware that houses the Cell Culture Module - Immune Response of Human Monocytes in Microgravity (CCM-Immune Response) and the Cell Culture Module - Effect of Microgravity on Wound Repair: In Vitro Model of New Blood Vessel Development (CCM-Wound Repair) experiments. The experiments were flown on STS118/13A.1 in August 2007.
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