Suppressed PHA Activation of T Lymphocytes in Simulated Microgravity Is Restored by Direct Activation of Protein Kinase C with Phorbol Ester

Various aspects of spaceflight, including microgravity, cosmic radiation, and physiological stress, may perturb immune function. We sought to understand the impact of microgravity alone on the cellular mechanisms critical to immunity. We utilized clinostatic RWV bioreactors that simulate aspects of microgravity to analyze the response of human PBMC to polyclonal activation. PHA responsiveness in the RWV was almost completely diminished. IL-2 and IFN-gamma secretion was reduced whereas IL- 1 beta and IL-6 secretion was increased, suggesting that monocytes may not be as adversely affected by simulated microgravity as T cells. Activation marker expression (CD25, CD69, CD71) was significantly reduced in RWV cultures. Furthermore, addition of exogenous IL-2 to these cultures did not restore proliferation. Reduced cell-cell and cell-substratum interactions may play a role in the loss of PHA responsiveness. However, PHA activation in Teflon culture bags that limit cell-substratum interactions did not suppress PHA activation. Furthermore, increasing cell density and, therefore, cell-cell interactions in the RWV cultures did not help restore PHA activation. However, placing PBMC within small collagen beads did partially restore PHA responsiveness. Activation of both PBMC and purified T cells with PMA and ionomycin was unaffected by RWV culture, indicating that signaling mechanisms downstream of PKC activation and calcium flux are not sensitive to simulated microgravity. Furthermore, submitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus, our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sensitive to simulated microgravity

Utilization of Microgravity Bioreactor for Differentiation and Growth of Human Vascular Endothelial Cells

The goal was to delineate mechanisms of genetic responses to angiogenic stimulation of human coronary arterial and dermal microvascular endothelial cells during exposure to microgravity. The NASA-designed rotating-wall vessel was used to create a three-dimensional culture environment with low shear-stress and microgravity simulating that in space. The primary specific aim was to determine whether simulated microgravity enhances endothelial cell growth and whether the growth enhancement is associated by augmented expression of Basic Fibroblast Growth Factor (BFGF) and c-fos, an immediate early gene and component of the transcription factor AP-1

Mineralized three-dimensional bone constructs

The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics

Mineralized Three-Dimensional Bone Constructs

The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics

Tissue Culture in Microgravity

Attempts to simulate normal tissue micro-environments in vitro have been thwarted by the complexity and plasticity of the extracellular matrix, which is important in regulating cytoskeletal and nuclear matrix proteins. Gravity is one of the problems, tending to separate components that should be kept together. For space shuttle experiments, NASA engineers devised a double-walled rotating bioreactor, which is proving to be a useful tissue culture device on earth as well as in space

Social Contact Patterns in Vietnam and Implications for the Control of Infectious Diseases

BACKGROUND: The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam. METHODS AND FINDINGS: A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R(0). CONCLUSIONS AND SIGNIFICANCE: This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data

Technological Innovations from NASA

The challenge of human space exploration places demands on technology that push concepts and development to the leading edge. In biotechnology and biomedical equipment development, NASA science has been the seed for numerous innovations, many of which are in the commercial arena. The biotechnology effort has led to rational drug design, analytical equipment, and cell culture and tissue engineering strategies. Biomedical research and development has resulted in medical devices that enable diagnosis and treatment advances. NASA Biomedical developments are exemplified in the new laser light scattering analysis for cataracts, the axial flow left ventricular-assist device, non contact electrocardiography, and the guidance system for LASIK surgery. Many more developments are in progress. NASA will continue to advance technologies, incorporating new approaches from basic and applied research, nanotechnology, computational modeling, and database analyses

Modeled Microgravity Inhibits Apoptosis in Peripheral Blood Lymphocytes

Impairment of the immunity in astronauts and cosmonauts even in short term flights is a recognized risk. Long term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Impairment of the immunity in space may be due tonumerous physiological changes caused by space-related factors, which in turn affect the immune system, or alternatively, it may be due to direct effects of different factors encountered in space on lymphoid cells and their interactions. Indeed, in modeled microgravity (MMG) experiments on Earth we and others showed that microgravity directly affects multiple lymphocyte functions. It interferes with expression of cell surface molecules, causes inhibition of lymphocyte locomotion, suppresses polyclopal and antigen-specific lymphocyte activation, selectively inhibits protein kinase C (PKC) isoforms. Some of these effects were also confirmed in cell culture experiments in real space conditions during Spacelab, Biokosmos and Shuttle Missions. The results of these studies, taken together, strongly indicated that microgravity interferes with fundamental biological processes associated with functional and structural changes in cell surface membranes, cell surface molecules and in their interaction. Based on the data and on their interpretation, we hypothesized that microgravity in addition to observed functional changes affects programmed cell death (PCD) in lymphocyte populations and that this mechanism could contribute to the impairment of the immunity

Frontiers of Life Sciences: The Human Exploration of the Moon and Mars

The rapid development of the productive processes after World War II extended human settlements into new ecological niches. Advances in Life Sciences played a decisive role supporting the establishment of human presence in areas of the planet where human life could have not existed otherwise. The evolution of life support systems, and the fabrication of new materials and technologies has enabled humans to inhabit Polar Regions, ocean surfaces and depths; and to leave Earth and occupy Low Earth Orbit. By the end of the 20 th Century, stations in the Antarctic and Arctic, off shore oil platforms, submarines, and space stations had become the ultimate demonstration of human ability to engineer habitats at Earth extreme environments and outer space. As we enter the 21st Century, the next development of human settlements will occur through the exploration of the Moon, Mars, and beyond. The major risks of space exploration derive from long exposure of humans and other life systems to radiation, microgravity, isolation and confinement, dependence on artificial life support systems, and unknown effects (e.g., altered magnetic fields, ultrahigh vacuum on bacteria, fungi, etc.). Countermeasures will require a complete characterization of human and other biological systems adaptation processes. To sustain life in transit and on the surface of the Moon and Mars will require a balance of spacecraft, cargo, astronaut crews, and the use of in situ resources. Limitations on the number of crewmembers, payloads, and the barrenness of the terrain require a novel design for the capabilities needed in transit and at exploration outpost sites. The planned destinations have resources that may be accessed to produce materials, food, shelter, power, and to provide an environment compatible with successful occupation of longterm exploration sites. Once more, the advancements of Life Sciences will be essential for the design of interplanetary voyages and planetary surface operations. This presentation delineates the role of Life Sciences and its frontiers, especially Cell Science, in the context of human exploration. Life support systems, food production, and medical equipment encompass many of vital aspects related to the new vision for NASA