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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1989

The effects of simulated hypogravity on murine bone marrow cells

Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

Lawless, Desales↗
NASA NTRS2003

Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left-ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05). INTERPRETATION: These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

NASA Discipline Cardiopulmonary↗
NASA NTRS2011

Microgravity-Enhanced Stem Cell Selection

Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in conventional bioreactors, stirring invokes deleterious forces that disrupt cell aggregation and results in cell death. First-generation rotating bioreactors provided rotation on the horizontal axis, which resulted in the suspension of cells without stirring, thus providing a suitable environment to propagate cells without sedimentation to a surface. The rotating wall bioreactors did not provide a way to remove air bubbles that were causing shear and disrupting 3D cultures. Johnson Space Center successfully engineered the hydrofocusing bioreactor (HFB) that resolved the problem of removing the air bubbles from the fluid medium of NASA's rotating-wall space bioreactors. The HFB uses the principle of hydrodynamic focusing that simultaneously produces a low-shear fluid culture environment and a variable hydrofocusing force that can control the movement, location, and removal of suspended cells, tissues, and air bubbles from the bioreactor. The HFB is a rotating, domeshaped cell culture vessel with a centrally located sampling port and an internal viscous spinner. The vessel and spinner can rotate at different speeds either in the same or opposite directions. Rotation of the vessel and viscous interaction at the spinner generate a hydrofocusing force. Adjusting the differential rotation rate between vessel and spinner controls the magnitude of the force.

Claudio, Pier Paolo↗
NASA NTRS1991

Electrophoresis experiments in microgravity

The use of the microgravity environment to separate and purify biological cells and proteins has been a major activity since the beginning of the NASA Microgravity Science and Applications program. Purified populations of cells are needed for research, transplantation and analysis of specific cell constituents. Protein purification is a necessary step in research areas such as genetic engineering where the new protein has to be separated from the variety of other proteins synthesized from the microorganism. Sufficient data are available from the results of past electrophoresis experiments in space to show that these experiments were designed with incomplete knowledge of the fluid dynamics of the process including electrohydrodynamics. However, electrophoresis is still an important separation tool in the laboratory and thermal convection does limit its performance. Thus, there is a justification for electrophoresis but the emphasis of future space experiments must be directed toward basic research with model experiments to understand the microgravity environment and fluid analysis to test the basic principles of the process.

Snyder, Robert S.↗
NASA NTRS2004

Hematopoietic Stem Cell Therapy to Countermeasure Cancer in Astronauts during Exploration of Deep Space

Exposure to cosmic radiation can cause chromosomal mutations, which may lead to cancer in astronauts engaged in space exploration. Therefore, our goals are to develop countermeasures to prevent space-induced cancer using hematopoietic stem cell therapy (HSCT) and gene therapy. This presentation focuses on HSCT for cancer. Our previous experiments on a simulated, space-induced immuno-deficiency model (mouse hind limb unloading ) indicated that transplanted hematopoietic stem cells (HSCs) could enhance the host's immunity by effectively eliminating bacterial infection (Ohi S, et. al. J Grav Physiol 10, P63-64, 2003; Ohi S, et. al. Proceedings of the Space Technology and Applications International Forum (STAIF) . American Institute of Physics, New York, pp. 938-950, 2004). Hence, we hypothesized that the HSCs might be effective in combating cancer as well. Studies of cocultured mouse HSCs with beta-galactosidase marked rat gliosarcoma spheroids (9L/lacZ), a cancer model, indicated antagonistic interactions , resulting in destruction of the spheroids by HSCs. Trypan Blue dye-exclusion assays were consistent with the conclusion. These results show potential usehlness of HSCT for cancer. Currently, the NASA Hydrodynamic Focusing Bioreactor (HFB), a space analog tissue/cell culture system, is being used to study invasion of the gliosarcoma (GS) spheroids into mouse brain with or without co-cultured HSCs. This may simulate the metastasis of gliosarcoma to brain. There is a tendency for the HSCs to inhibit invasion of GS spheroids into brain, as evidenced by the X-gal staining.

Ohi, S.↗
NASA NTRS1999

Novel Approaches to Cellular Transplantation from the US Space Program

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

Pellis, Neal R.↗
NASA NTRS1997

Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

NASA Discipline Developmental Biology↗
NASA NTRS2015

Methods for Stem Cell Production and Therapy

The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

Claudio, Pier Paolo↗
NASA NTRS1989

The pituitary growth hormone cell in space

Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

Hymer, Wesley C.↗
NASA NTRS2001

Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

Non-NASA Center↗
NASA NTRS1997

Biomaterials for tissue engineering: summary

This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

Non-NASA Center↗
NASA NTRS1996

STS-79 Flight Day 5

On this fifth day of the STS-79 mission, the flight crew, Cmdr. William F. Readdy, Pilot Terrence W. Wilcutt, Mission Specialists, Thomas D. Akers, Shannon Lucid, Jay Apt, and Carl E. Walz, in the first full day of joint Shuttle/Mir operations begin in with the transfer of a biotechnology investigation and logistical supplies from Atlantis to Mir. The Biotechnology System, an investigation that will study the long-term development of cartilage cells in microgravity, was transported to Mir early this morning. During his planned four-month stay on Mir, John Blaha will take weekly samples of the culture which may provide researchers with information on engineering cartilage cells for possible use in transplantation. They also took time out of their schedules to talk with Good Morning America's Elizabeth Vargas in a brief interview. Prior to beginning the day's transfer activities, all nine astronauts and cosmonauts participated in a joint planning session to outline the day's schedule.

Source record↗
NASA NTRS1992

Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels

A new low shear stress microcarrier culture system has been developed at NASA's Johnson Space Center that permits three-dimensional tissue culture. Two established human colon adenocarcinoma cell lines, HT-29, an undifferentiated, and HT-29KM, a stable, moderately differentiated subline of HT-29, were grown in new tissue culture bioreactors called Rotating-Wall Vessels (RWVs). RWVs are used in conjunction with multicellular cocultivation to develop a unique in vitro tissue modeling system. Cells were cultivated on Cytodex-3 microcarrier beads, with and without mixed normal human colonic fibroblasts, which served as the mesenchymal layer. Culture of the tumor lines in the absence of fibroblasts produced spheroidlike growth and minimal differentiation. In contrast, when tumor lines were co-cultivated with normal colonic fibroblasts, initial growth was confined to the fibroblast population until the microcarriers were covered. The tumor cells then commenced proliferation at an accelerated rate, organizing themselves into three-dimensional tissue masses that achieved 1.0- to 1.5-cm diameters. The masses displayed glandular structures, apical and internal glandular microvilli, tight intercellular junctions, desmosomes, cellular polarity, sinusoid development, internalized mucin, and structural organization akin to normal colon crypt development. Differentiated samples were subjected to transmission and scanning electron microscopy and histologic analysis, revealing embryoniclike mesenchymal cells lining the areas around the growth matrices. Necrosis was minimal throughout the tissue masses. These data suggest that the RWV affords a new model for investigation and isolation of growth, regulatory, and structural processes within neoplastic and normal tissue.

Colonic Neoplasms/pathology↗
NASA NTRS1977

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

Rubin, A. L.↗
NASA NTRS1977

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity, phase 3

Electrophoretic mobilities (EPM) of peripheral lymphocytes were studied from normal subjects, chronic hemodialysis patients and kidney transplant recipients. A technique to separate B lymphocytes and null cells from non-T lymphocyte preparation was developed. The experiments were designed to determine which subpopulation of the non-T lymphocytes is primarily affected and shows a decreased EPM in chronic hemodialysis patients and kidney transplant recipients.

Rubin, A. L.↗
NASA NTRS1992

The effects of interferon-alpha/beta in a model of rat heart transplantation

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

NASA Discipline Regulatory Physiology↗
NASA NTRS1977

Benefit evaluation of space processing of biological materials

A rational analytical basis for the evaluation of potential benefits of space processing of biological materials is described. A preliminary evaluation of three candidate space processed biological materials was accomplished. Materials investigated were human lymphocytes, urokinase, and Beta cells. Separation of lymphocyte groups was considered in order to improve the matching of donors and recipients for kidney transplantation, while urokinase was examined in regard to treatment of thromboembolic diseases. Separation of Beta cells was studied since it could provide a highly effective means for the treatment of juvenile-onset diabetes.

Source record↗
NASA NTRS1975

A survey of the economics of materials processing in space

A survey of the economics of space materials processing has been performed with the objectives of identifying those areas of space materials processing that give preliminary indication of significant economic potential, and to identify possible approaches to quantify the economic potential. It is concluded that limited economic studies have been performed to date, primarily in the area of the processing of inorganic materials, but that the economics of space processing of biological material has not received adequate attention. Specific studies are recommended to evaluate the economic impact of human lymphocyte subgroup separation on organ transplantation, and on the separation and concentration of urokinase producing cells.

Miller, B. P.↗