Space Tissue Loss is a DoD Space Test Program payload flying both DoD and NASA science that uses cell and tissue cultures in microgravity to study the effects of tissue regeneration and wound healing in space.Principal Investigator(s)
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
National Aeronautics and Space Administration (NASA)Sponsoring Organization
National Laboratory - Department of Defense (NL-DoD)Research Benefits
Information PendingISS Expedition Duration
March 2011 - September 2011Expeditions Assigned
27/28Previous 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.
Previous studies suggest that continuous exposure to microgravity during spaceflight develops an immunocompromised host, thus significantly delaying the wound healing process. Compromised healing cascade meets further challenges as microgavity tends to have a complementary effect on bacterial cell growth. Comprehensive knowledge of the healing etiology submitted to the dual stressors is eminent, but presently elusive. Towards this objective, an in vitro model of endotoxin assaulted dermal cellular system is proposed to investigate under altered gravitational force.
Briefly, the endothelial cells will be seeded onto hollow-fiber bioreactors and perfused. Lippopolysaccharide (LPS), an endotoxin commonly associated with gram negative bacteria, will be injected into the test samples during the flight and the reaction will be stopped at two different time intervals. High throughput gene, microRNA, metabolite and protein expression analyses will be carried out to characterize the molecular signatures associated with the temporal response of the gravity-compromised endothelial cells towards the endotoxin.
Identified signatures at transcriptomic, miRNA, proteomic and metabolomic levels will be further compared with the database generated through the ground level study associated with similar cell based insult.
The proposed experiments will expand the system biological knowledge in the following aspects associated with in vitro wound model subjected to microgravity:
1. Omics-based temporal molecular markers/ therapeutic targets associated with endotoxin induced dermal blood microvascular endothelial cell injury.
2. Key biological networks/ nodes/ downstream ?disease footprints? associated with LPS-induced endothelial cell injury.
3. A comparative analysis of wound model developed in space and at ground to identify factors that are key regulators or components of differentiation.
The Cell Culture Module (CCM) hardware used in STL 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. STL is made up of three experiments that will be conducted inside the CCM. 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.
Prolonged residence in a space shuttle causes immunocompromisation; therefore the astronauts not only suffer from a delayed healing process, they also become particularly vulnerable to bacterial infection. This study is designed to identify certain early molecular signatures and/or therapeutic targets associated with the compromised healing cascade.Earth Applications
Wound healing is considered a major clinical challenge in surgical and military units; the related concerns have been mounting recently, triggered by an aging population and increasing rates of diabetes, obesity and cancer treatment side effects. To better understand the physiological cascade of the healing model, the present plan intends to temporally obtain in vitro biological samples associated with endotoxin insulted dermal cells and identify molecular signatures using an integrated pan-omics platform. We project that the earth based pan-omic study may reveal true EARLY (or "immediate onset") indicators of the healing cascade; but, perhaps more importantly, a demonstrable understanding of the regulatory nodes/networks cascading into successful wound healing.
Four rails with individual flow paths and bioreactors will be housed inside the CCM hardware. Two rails will be used for the NASA investigator and two rails will be shared between the DoD investigators. The configuration will allow for redundancy in experiments, increasing the probability of successful tests and samples returning to earth for analysis.Operational Protocols
The STL investigation is self contained and requires crew interaction for activation, status checks, and re-entry. Rails will contain cell lines treated with different agents. Following the return to Earth, the rails will be returned to the investigator for in-depth analysis.