NASA Human Research Program (HRP). International Space Station Medical Project (ISSMP)

This viewgraph presentation describes the various flight investigations performed on the International Space Station as part of the NASA Human Research Program (HRP). The evaluations include: 1) Stability; 2) Periodic Fitness Evaluation with Oxygen Uptake Measurement; 3) Nutrition; 4) CCISS; 5) Sleep; 6) Braslet; 7) Integrated Immune; 8) Epstein Barr; 9) Biophosphonates; 10) Integrated cardiovascular; and 11) VO2 max

Multidimensional Processing and Visual Rendering of Complex 3D Biomedical Images

The proposed technology uses advanced image analysis techniques to maximize the resolution and utility of medical imaging methods being used during spaceflight. We utilize COTS technology for medical imaging, but our applications require higher resolution assessment of the medical images than is routinely applied with nominal system software. By leveraging advanced data reduction and multidimensional imaging techniques utilized in analysis of Planetary Sciences and Cell Biology imaging, it is possible to significantly increase the information extracted from the onboard biomedical imaging systems. Year 1 focused on application of these techniques to the ocular images collected on ground test subjects and ISS crewmembers. Focus was on the choroidal vasculature and the structure of the optic disc. Methods allowed for increased resolution and quantitation of structural changes enabling detailed assessment of progression over time. These techniques enhance the monitoring and evaluation of crew vision issues during space flight

High aspect reactor vessel and method of use

An improved bio-reactor vessel and system useful for carrying out mammalian cell growth in suspension in a culture media are presented. The main goal of the invention is to grow and maintain cells under a homogeneous distribution under acceptable biochemical environment of gas partial pressures and nutrient levels without introducing direct agitation mechanisms or associated disruptive mechanical forces. The culture chamber rotates to maintain an even distribution of cells in suspension and minimizes the length of a gas diffusion path. The culture chamber design is presented and discussed

HRP Data Accessibility Current Status

Overview of talk: a) Content of Human Life Science data; b) Data archive structure; c) Applicable legal documents and policies; and d) Methods for data access. Life Science Data Archive (LSDA) contains research data from NASA-funded experiments, primarily data from flight experiments and ground analog data collected at NASA facilities. Longitudinal Study of Astronaut Health (LSAH) contains electronic health records (medical data) of all astronauts, including mission data. Data are collected for clinical purposes. Clinical data are analyzed by LSAH epidemiologists to identify trends in crew health and implement changes in pre-, in-, or post-flight medical care

Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in and postflight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deepspace exploration missions

ISS Science: Status of Implementation Constraints

With the completion of the International Space Station imminent, there are many opportunities for scientific experiments. There are also constraints that must be understood. This viewgraph presentation reviews some of the opportunities will be available and constraints that must be imposed. The scientist designing the experiments for the ISS, must understand and consider these factors and plan the design to minimize the impact of these constraints

Whole Blood Activation Results in Enhanced Detection of T Cell and Monocyte Cytokine Production by Flow Cytometry

An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a wholeblood activation culture has been described. We compared whole blood culture to standard PBMC culture and determined the individual cytokine secretion patterns for both T cells and monocytes via flow cytometry. For T cells cytokine assessment following PMA +ionomycin activation: (1) a significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture; (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. In addition, a four-color cytometric analysis was used to allow accurate phenotyping and quantitation of cytokine producing lymphocyte populations. Using this technique we found IFNgamma production to be significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines in conjunction with CD 14. The cytokine pairs used for analysis were IL-1a/IL-12, and IL-10ITNFa. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFalpha equally well in both culture systems. Monocyte production of IL-10 was significantly elevated following whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent functionally different monocyte subsets with distinct functions. Whole blood culture eliminates the need to purify cell populations prior to culture and may have significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. It is likely that the altered cytokine production observed following whole blood culture more accurately represents the in-vivo immune balance

Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent distinct monocyte subsets with unique functions. CONCLUSIONS: Whole blood culture eliminates the need to purify cell populations prior to culture and may have Significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. In this study, alterations in cytokine production are demonstrated between whole blood and PBMC activation. It is likely that whole blood activation more accurately represents the in-vivo immune balance than PBMC activation

Medical and Scientific Evaluations aboard the KC-135. Microgravity-Compatible Flow Cytometer

A spaceflight-compatible flow cytometer would be useful for the diagnosis of astronaut illness during long duration spaceflight and for conducting in-flight research to evaluate the effects of microgravity on human physiology. Until recently, the primary limitations preventing the development of a spaceflight compatible flow cytometer have been largely mechanical. Standard commercially available flow cytometers are large, complex instruments that use high-energy lasers and require significant training to operate. Standard flow cytometers function by suspending the particles to be analyzed inside a sheath fluid for analysis. This requires the presence of several liters of sheath fluid for operation, and generates a corresponding amount of liquid hazardous waste. The particles are then passed through a flow cell which uses the fluid mechanical property of hydrodynamic focusing to place the cells in single-file (laminar flow) as they pass through a laser beam for scanning and evaluation. Many spaceflight experiments have demonstrated that fluid physics is dramatically altered in microgravity (MSF [Manned Space Flight] Fluid Physics Data Sheet-August 1997) and previous studies have shown that sheath-fluid based hydrodynamic focusing may also be altered during microgravity (Crucian et al, 2000). For these reasons it is likely that any spaceflight compatible design for a flow cytometer would abandon the sheath fluid requirement. The elimination of sheath fluid would remove both the problems of weight associated with large volumes of liquids as well as the large volume of liquid waste generated. It would also create the need for a method to create laminar particle flow distinct from the standard sheath-fluid based method. The spaceflight prototype instrument is based on a recently developed commercial flow cytometer possessing a novel flow cell design that creates single-particle laser scanning and evaluation without the need for sheath-fluid based hydrodynamic focusing. This instrument also possesses a number of design advances that make it conditionally microgravity compatible: it is highly miniaturized and lightweight, uses a low energy diode laser, has a small number of moving parts, does not use sheath fluid and does not generate significant liquid waste. Although possessing certain limitations, the commercial cytometer functions operationally like a standard bench top laboratory flow cytometer, aspirating liquid particle samples and generating histogram or dot-plot data in standard FCS file format. In its current configuration however, the cytometer is limited to three parameter/two-color capability (two color PMTs + forward scatter), does not allow compensation between colors, does not allow linear analysis and is operated by rather inflexible software with limited capabilities. This is due to the fact that the cytometer has been designed and marketed as an instrument specific to a few particular assays, not as a multipurpose cytometer

The Human in Space: Lesson from ISS

This viewgraph presentation reviews the lessons learned from manned space flight on the International Space Station. The contents include: 1) Overview of space flight effects on crewmembers; 2) General overview of immune system; 3) How does space flight alter immune system? 4) What factors associated with space flight inteact with crewmember immune function and impact health risks? 5) What is the current understanding of space flight effects on the immune system? and 6) Why should NASA be interested in immunology? Why is it significant