Radiation Effects on Tissue Differentiation in a 3-D Organotypic Aerodigestive Tract Model

No abstract availabl

A Bi-Exponential Repair Algorithm for Radiation-Induced Double-Strand Breaks: Application to Chromosome Aberrations

Chromosome aberrations (CAs) are one of the effects of radiation exposure and are used as a biomarker. A new simulation program, named RITCARD (Radiation induced tracks, chromosome aberrations, repair, and damage) was developed to simulate radiation-induced CA. RITCARD is used with the program RITRACKS (Relativistic Ion Tracks), which simulates the radiation tracks. The restitution kinetics algorithm presented here is a significant improvement over the one used in the first version. Simulations of radiation-induced CA were performed for several ion types and mixed irradiation fields. These simulations will be useful to help interpreting experiments of galactic cosmic rays (GCR) simulator

Space Radiation and Risks to Human Health

The radiation environment in space poses significant challenges to human health and is a major concern for long duration manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as xrays and gammarays. Galactic cosmic rays consist of high energy and high mass nuclei as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. The major health issues of concern are the risks of radiation carcinogenesis, acute and late decrements to the central nervous system, degenerative tissue effects such as cardiovascular disease, as well as possible acute radiation syndromes due to an unshielded exposure to a large solar particle event. The NASA Human Research Program's Space Radiation Program Element is focused on characterization and mitigation of these space radiation health risks along with understanding these risks in context of the other biological stressors found in the space environment. In this overview, we will provide a description of these health risks and the Element's research strategies to understand and mitigate these risks

An Overview of NASA's Risk of Cardiovascular Disease from Radiation Exposure

The association between high doses of radiation exposure and cardiovascular damage is well established. Patients that have undergone radiotherapy for primary cancers of the head and neck and mediastinal regions have shown increased risk of heart and vascular damage and long-term development of radiation-induced heart disease [1]. In addition, recent meta-analyses of epidemiological data from atomic bomb survivors and nuclear industry workers has also shown that acute and chronic radiation exposures is strongly correlated with an increased risk of circulatory disease at doses above 0.5 Sv [2]. However, these analyses are confounded for lower doses by lifestyle factors, such as drinking, smoking, and obesity. The types of radiation found in the space environment are significantly more damaging than those found on Earth and include galactic cosmic radiation (GCR), solar particle events (SPEs), and trapped protons and electrons. In addition to the low-LET data, only a few studies have examined the effects of heavy ion radiation on atherosclerosis, and at lower, space-relevant doses, the association between exposure and cardiovascular pathology is more varied and unclear. Understanding the qualitative differences in biological responses produced by GCR compared to Earth-based radiation is a major focus of space radiation research and is imperative for accurate risk assessment for long duration space missions. Other knowledge gaps for the risk of radiation-induced cardiovascular disease include the existence of a dose threshold, low dose rate effects, and potential synergies with other spaceflight stressors. The Space Radiation Program Element within NASA's Human Research Program (HRP) is managing the research and risk mitigation strategies for these knowledge gaps. In this presentation, we will review the evidence and present an overview of the HRP Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Development of an Autonomous, Dual Chamber Bioreactor for the Growth of 3-Dimensional Epithelial-Stromal Tissues in Microgravity

We are developing a novel, autonomous bioreactor that can provide for the growth and maintenance in microgravity of 3D organotypic epithelialstromal cultures that require an airliquid interface. These complex 3D tissue models accurately represent the morphological features, differentiation markers, and growth characteristics observed in normal human epithelial tissues, including the skin, esophagus, lung, breast, pancreas, and colon. However, because of their precise and complex culture requirements, including that of an airliquid interface, these 3D models have yet to be utilized for life sciences research aboard the International Space Station. The development of a bioreactor for these cultures will provide the capability to perform biological research on the ISS using these realistic, tissuelike human epithelialstromal cell models and will contribute significantly to advances in fundamental space biology research on questions regarding microgravity effects on normal tissue development, aging, cancer, and other disease processes. It will also allow for the study of how combined stressors, such as microgravity with radiation and nutritional deficiencies, affect multiple biological processes and will provide a platform for conducting countermeasure investigations on the ISS without the use of animal models. The technology will be autonomous and consist of a cell culture chamber that provides for airliquid, liquidliquid, and liquidair exchanges within the chambers while maintaining the growth and development of the biological samples. The bioreactor will support multiple tissue types and its modular design will provide for incorporation of addon capabilities such as microfluidics drug delivery, media sampling, and in situ biomarker analysis. Preliminary flight testing of the hardware will be conducted on a parabolic platform through NASA's Flight Opportunities Program

Overview of Space Radiation Health Risks with a Focus on Radiation Induced Cardiovascular Diseases

No abstract availabl

Controlled delivery of angiogenic and osteogenic growth factors for bone regeneration

This research introduces a delivery system for the release of an angiogenic and an osteogenic growth factor to address the inability of large bone defects to sufficiently heal. These critical size defects (CSDs) affect approximately one million patients annually. Current treatments rely on the use of bone grafts or permanent orthopedic implants; alternatively, tissue engineering strategies utilize a combination of biomaterials for the delivery of osteoprogenitor cells and osteogenic growth factors. However, few studies address the importance of angiogenesis for bone regeneration, particularly in CSDs which require the presence of an underlying vasculature to recruit and support osteoprogenitor cells within the large defect. We hypothesized that controlled delivery of an angiogenic growth factor, vascular endothelial growth factor (VEGF), and an osteogenic growth factor, bone morphogenetic protein-2 (BMP-2), would demonstrate a compounded effect to induce the closure of CSDs. Both growth factors were delivered from gelatin microparticles incorporated within a porous polymer scaffold. In vitro studies showed that VEGF and BMP-2 release kinetics were affected by the extent of gelatin crosslinking, but growth factor dose was found to affect release only minimally for the doses investigated. Additionally, gelatin type was also found to affect the release profiles of BMP-2. Early delivery of VEGF and minimal burst release and sustained delivery of BMP-2 were attained in vitro and in vivo by using acidic and basic gelatin, and low and high gelatin crosslinking, respectively. A critical size rat cranial defect was also used to evaluate the regenerative potential of this dual delivery system in vivo. At 4 weeks, there was no difference in blood vessel formation between groups, but dual release groups exhibited significantly higher bone formation at 4 weeks along with increased bony bridging at 12 weeks. Bone formation at 12 weeks in the dual release and BMP-2-only groups were significantly higher than in VEGF-only groups or blank scaffolds. These results suggest a synergistic effect for dual release at early time periods and indicate faster healing times at later periods. The studies presented here demonstrate the potential of this unique dual release system for use in strategies for bone regeneration

Mitigation Strategies for Space Radiation Health Risks

Astronauts embarking on missions beyond low Earth orbit (LEO) will be exposed to a radiation field that may increase the risks of developing cancer, cardiovascular diseases, central nervous system disorders, and immune decrements. Operational parameters will be the primary determinants of crew radiation exposure. NASA uses integrated design tools and risk models to optimize these parameters to minimize radiation exposure. NASA is also considering medical countermeasures (MCMs) to reduce radiation-associated health risks. MCMs for potential use in space-based applications can be developed from a variety of sources, including: a) population-based chemoprevention trials against targeted diseases b) drug development efforts focused on treating acute effects from accidental radiation exposures c) drug development to mitigate side effects of radiotherapy d) mechanistic studies of distinct damage caused by high charge (Z) and energy (HZE) radiation. Use of agents developed for other applications, or repurposed, is advantageous because long-term safety in humans is already established

A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron)