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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS1980

Late degeneration in rabbit tissues after irradiation by heavy ions

Results are presented for investigations of the late effects of heavy-ion irradiation on rabbit tissues which were undertaken to assess the hazards associated with the long-term exposure of humans to heavy ions in space during such activities as the construction of solar power stations or voyages to Mars. White rabbits approximately six weeks old were exposed to various doses of collimated beams of 400-MeV/n Ne ions, 570 MeV/n Ar ions and Co-60 gamma rays directed through both eyes, and the responses of the various tissues (hair follicles, skin, cornea, lens, retina, Harderian glands, bone and forebrain) were examined. Proliferating tissues are found to exhibit high damage levels in the early and late periods following irradiation, while terminally differentiating tissues repond to radiation most intensely in the late period, years after irradiation, with no intermediate recovery. The results obtained from rabbits are used to predict the occurrence of late tissue degeneration in the central nervous system, terminally differentiating systems and stem cells of humans one or more decades following exposure to radiation levels anticipated during long-duration space flights. The studies also indicate that tissues may be prematurely aged in the sense that tissue life spans may be shortened without the development of malignancies.

Lett, J. T.↗
NASA NTRS1983

Cataractogenesis from high-LET radiation and the Casarett model

The long-term effects on specific animal tissues of exposure to heavy ion irradiation are studied in experiments on cataractogenesis in mice and rabbits. Five groups of rabbits at ages from 8 weeks to 5.3 years were irradiated to a dose of 9.0 Gy of Bragg plateau Ne-20 ions, while mice were exposed to single and total fractionated doses of 4.17 Gy gamma rays or 0.40 to 1.20 Gy of C-12, Ne-20 or Ar-40 particles. Measurements of lens opacities over time show that in the year since irradiation, cataractogenesis is delayed and less severe in rabbits irradiated at age 6 months compared to younger animals, although it is possible that the late effects in adults will surpass those found in the young. The fractionation of the total dose of gamma rays in mice is observed to lead to a marked reduction in the extent of lens opacity after one year, while fractionated heavy ion doses caused a greater degree of posterior lens opacification. Evaluations of the effects of the LET of different ions on cataractogenesis are consistent with RBEs of about 5, 3 and 1-2 for Ar-40, Ne-20 and C-12 ions, respectively. Results thus support the Casarett model of radiation damaging stem cell populations that are not necessarily part of the vasculature.

Cox, A. B.↗
NASA NTRS1999

Investigation of Point Doppler Velocimetry (PDV) for Transition Detection in Boundary Layers

A two component Point Doppler Velocimetry (PDV) system has been developed and tested. Improvements were made to an earlier PDV system, in terms of experimental techniques, as well as the data acquisition and reduction software. Measurements of the streamwise and spanwise mean and fluctuating velocities for flows from a rectangular channel and over an NACA 0012 airfoil were made, and the data were compared against hot wire data. The closest to the airfoil surface that PDV measurements could be made was on the order of 0.005 m(0.2", z/c = 0.0169). When the PDV and hot wire data were compared, the time traces for each appeared similar. The mean velocities agreed to within plus or minus 2 m/sec, while the RMS velocities agreed to plus or minus 0.4 m/sec. While the PDV time autocorrelations agreed with those of the hot wire data, the PDV power spectral densities were noisier above 750 Hz. A major source of error in these experiments was determined to be the drifting of the iodine cell stem temperatures. While the stem temperatures were controlled to within plus or minus 0.1 C, this could lead to a frequency shift of as much as 6 MHz, which translates into an error of 1.6 m/sec for the back scatter channel, and up to 6.9 m/sec for the forward scatter channel. These error estimates are consistent with the observed error magnitudes.

Kuhlman, John M.↗
NASA NTRS2000

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

NASA Discipline Radiation Health↗
NASA NTRS2000

Leech segmental repeats develop normally in the absence of signals from either anterior or posterior segments

We have investigated whether the development of segmental repeats is autonomous in the embryo of the leech Helobdella robusta. The segmental tissues of the germinal band arise from progeny of five stem cells called teloblasts. Asymmetric divisions of the teloblasts form chains of segment founder cells (called primary blast cells) that divide in a stereotypical manner to produce differentiated descendants. Using two distinct techniques, we have looked for potential interactions between neighboring blast cell clones along the anterior-posterior axis. In one technique, we prevented the birth of primary blast cells by injection of DNase I into the teloblast, thereby depriving the last blast cell produced before the ablation of its normal posterior neighbors. We also ablated single blast cells with a laser microbeam, which allowed us to assess potential signals acting on either more anterior or more posterior primary blast cell clones. Our results suggest that interactions along the anterior-posterior axis between neighboring primary blast cell clones are not required for development of normal segmental organization within the blast cell clone. We also examined the possibility that blast cells receive redundant signals from both anterior and posterior neighboring clones and that either is sufficient for normal development. Using double blast cell laser ablations to isolate a primary blast cell clone by removal of both its anterior and its posterior neighbor, we found that the isolated clone still develops normally. These results reveal that the fundamental segmental repeat in the leech embryo, the primary blast cell clone, can develop normally in the apparent absence of signals from adjacent repeats along the anterior-posterior axis.

NASA Discipline Evolutionary Biology↗
NASA NTRS2001

Bioengineered anterior cruciate ligament

The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Optimally, the mechanical forces to which the matrix is subjected mimic mechanical stimuli experienced by an anterior cruciate ligament in vivo. This is accomplished by delivering the appropriate combination of tension, compression, torsion, and shear, to the matrix. The bioengineered ligament which is produced by this method is characterized by a cellular orientation and/or matrix crimp pattern in the direction of the applied mechanical forces, and also by the production of collagen type I, collagen type III, and fibronectin proteins along the axis of mechanical load produced by the mechanical forces. Optimally, the ligament produced has fiber bundles which are arranged into a helical organization. The method for producing an anterior cruciate ligament can be adapted to produce a wide range of tissue types ex vivo by adapting the anchor size and attachment sites to reflect the size of the specific type of tissue to be produced, and also adapting the specific combination of forces applied, to mimic the mechanical stimuli experienced in vivo by the specific type of tissue to be produced. The methods of the present invention can be further modified to incorporate other stimuli experienced in vivo by the particular developing tissue, some examples of the stimuli being chemical stimuli, and electro-magnetic stimuli. Some examples of tissue which can be produced include other ligaments in the body (hand, wrist, elbow, knee), tendon, cartilage, bone, muscle, and blood vessels.

Altman, Gregory↗
NASA NTRS2010

The Road to NASA

This slide presentation describes the career path and projects that the author worked on during her internship at NASA. As a Graduate Student Research Program (GSRP) participant the assignments that were given include: Human Mesenchymal Stem Cell Research, Spaceflight toxicology, Lunar Airborne Dust Toxicity Advisory Group (LADTAG) and a special study at Devon Island.

Meyers, Valerie↗
NASA NTRS2011

NASA Tech Briefs, June 2011

Topics covered include: Wind and Temperature Spectrometry of the Upper Atmosphere in Low-Earth Orbit; Health Monitor for Multitasking, Safety-Critical, Real-Time Software; Stereo Imaging Miniature Endoscope; Early Oscillation Detection Technique for Hybrid DC/DC Converters; Parallel Wavefront Analysis for a 4D Interferometer; Schottky Heterodyne Receivers With Full Waveguide Bandwidth; Carbon Nanofiber-Based, High-Frequency, High-Q, Miniaturized Mechanical Resonators; Ultracapacitor-Based Uninterrupted Power Supply System; Coaxial Cables for Martian Extreme Temperature Environments; Using Spare Logic Resources To Create Dynamic Test Points; Autonomous Coordination of Science Observations Using Multiple Spacecraft; Autonomous Phase Retrieval Calibration; EOS MLS Level 1B Data Processing Software, Version 3; Cassini Tour Atlas Automated Generation; Software Development Standard Processes (SDSP); Graphite Composite Panel Polishing Fixture; Material Gradients in Oxygen System Components Improve Safety; Ridge Waveguide Structures in Magnesium-Doped Lithium Niobate; Modifying Matrix Materials to Increase Wetting and Adhesion; Lightweight Magnetic Cooler With a Reversible Circulator; The Invasive Species Forecasting System; Method for Cleanly and Precisely Breaking Off a Rock Core Using a Radial Compressive Force; Praying Mantis Bending Core Breakoff and Retention Mechanism; Scoring Dawg Core Breakoff and Retention Mechanism; Rolling-Tooth Core Breakoff and Retention Mechanism; Vibration Isolation and Stabilization System for Spacecraft Exercise Treadmill Devices; Microgravity-Enhanced Stem Cell Selection; Diagnosis and Treatment of Neurological Disorders by Millimeter-Wave Stimulation; Passive Vaporizing Heat Sink; Remote Sensing and Quantization of Analog Sensors; Phase Retrieval for Radio Telescope and Antenna Control; Helium-Cooled Black Shroud for Subscale Cryogenic Testing; Receive Mode Analysis and Design of Microstrip Reflectarrays; and Chance-Constrained Guidance With Non-Convex Constraints.

Source record↗
NASA NTRS2014

Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Schmidt, M. A.↗
NASA NTRS2017

Novel Approach to Quantification of Telomere Length with Direct Nanopore Sequencing and PCR Amplification

The ends of human chromosomes contain telomeres, or tandem arrays of repeating DNA sequences capped by multiple associated proteins that protect chromosomal ends from degradation. Telomeres function to preserve genomic stability by preventing natural chromosomal ends from being recognized as broken DNA double-strand breaks and triggering inappropriate DNA damage responses. Mounting evidence shows telomere length is an inherited trait that decreases with cellular division and normal aging. In addition, telomere length also appears to be influenced by other factors such as cellular oxidative stress, radiation and mechanical unloading of tissues as in microgravity. To measure these potential effects of the space environment on telomere lengths and cellular aging and regenerative potential we developed a novel telomere measurement approach based on nanopore sequencing of PCR amplified bar-coded chromosome termini. Specifically, telomeres can be directly enriched using barcode sequences ligated to the end of a free end- repaired telomere using the WetLab-2 facility SmartCycler on ISS. Prior to the ligation and amplification protocol a proteinase K digestion of capping proteins followed by a single 95-degree C heat denaturation of the protease is included. After digestion and bar-code ligation, PCR amplification will initiate with the ligated barcoded sequence, suppressing amplification of intra-genomic fragments and resulting in long read barcoded telomere amplicons including the nanopore motor protein sequences. Purified PCR amplicons are then used for nanopore sequencing library generation by simple addition of motor proteins and sequencing library is loaded into the MinION nanopore DNA-sequencer. Amplicon sequence reads from the nanopore device can be base-called quickly on ISS due to barcoding ligation and subsequent PCR amplification enhancing the telomere sequence resolution. If successfully implemented on ISS this technique will provide a novel means of measuring regenerative ability of somatic stem cells in astronauts, and of determining whether spaceflight in microgravity alters their telomere lengths and causes premature cellular aging.

Ma, Kristin R.↗
NASA NTRS2018

Prevention of Spaceflight-Induced Bone Loss: A Promising Dietary Countermeasure

Space radiation is one of the challenges for long-term spaceflight, especially for missions beyond low Earth Orbit. We have shown that a diet composed of 25% dried plum (DP) prevents radiation-induced bone loss. The DP diet fully protected the cancellous bone microarchitecture of mice exposed to ionizing radiation (gamma, proton, and HZE). In particular relevant to space radiation, we showed that the DP diet prevents bone loss due to 1Gy of sequential exposure of proton (1H, low linear energy transfer -LET-), and 1Gy of iron (56Fe, high-LET). In addition, total body exposure to 1Gy of HZE radiation (56Fe) impaired the osteoprogenitors in mice fed the control diet, as indicated by decreased osteoblast mineralization. In contrast, marrow stem cells from mice fed the DP did not exhibit these deficits. Based on these promising results supporting DP as a countermeasure to prevent space radiation induced-tissue damage, we conducted additional studies to combine radiation and simulated microgravity. We exposed skeletally mature male mice to simulated microgravity (using hindlimb unloading, HU) or total body irradiation (TBI, 2Gy 137Cs) or in combination (HU+TBI). We observed bone loss in the mice fed the control diet (CD) exposed to simulated spaceflight, as measured by cancellous bone microarchitecture parameters such as percent bone volume (BV/TV). In contrast, mice fed the DP diet did not exhibit similar bone loss with either treatments (HU or TBI) or combined (HU+TBI) as seen in most parameters. This was observed in both long bones (tibia) and axial bones (vertebrae). Furthermore, preliminary data shows that pre-feeding with the DP diet attenuates the HU-induced decrement in bone-forming osteoblasts colony counts and mineralization capacity of the osteoprogenitor cells. We also performed DP feeding at lower doses (5%, 10%) and found that these doses are less effective in preventing the radiation-induced bone loss. All our studies with the DP diet as a countermeasure were done with a period of pre-feeding ranging from 14 to 21 days before irradiation, and in order to test the capacity of the DP diet as a countermeasure provided after exposure to radiation, we exposed mice to 2Gy gamma radiation and then provided the DP diet 24 hours post-IR. Preliminary data indicates that DP mitigated the radiation-induced deficits in certain cancellous bone structural parameters. Finally, we showed that mice fed with the control diet (CD) increased oxidative damage in the serum after radiation exposure, whereas mice fed the DP diet do did not show such an increase. In summary, the DP diet is a promising countermeasure for spaceflight-induced tissue damage.

Schreurs, Ann-Sofie↗
NASA NTRS2021

Rodent Research in Space: A Decadal Research Campaign

Studying the physiological effects of spaceflight in rodents is imperative to our understanding of adaptation and to providing countermeasures. We posit that studies of the reproductive system, development, stem cells, and behavior/cognition are critically important and provide outstanding opportunities as these are sentinel tissues and systems for radiation exposure and overall health. To improve understanding of the environmental stressors (weightlessness, space radiation, isolation/confinement) that impact space travelers, rodent research should be continued within and extended beyond LEO.

rodent research spaceflight↗
NASA NTRS2024

Biofabrication in Space - A Perspective

Human exploration of Mars is one of the primary goals of NASA. A three-year human exploration mission to Mars is a viable design reference mission (Design Reference Mission). If we are sending a four member crew, comprehensive understanding of the health conditions of the crew is important. Based on the biomedical results of long-duration crew members at ISS, and during gravitational transitions, a few maladaptation have been observed. Discovering the root-cause of these aberrations and finding suitable mitigations at the molecular and cellular levels are of importance for a successful mission. Developing and executing the technologies to carry out tissue generation in space as well as the development of an analog hardware for tissue generation under terrestrial conditions will be discussed. These tissues were typically used to develop disease models and drug toxicology studies for several weeks and many other applications. The significant progress made during the last two decades have unfolded developments in organ generation, stem cell generation in space. When you remove the gravitational force during these cellular building processes while in space, other forces like surface tension, intermolecular forces, Coriolis force, loss of convection, reduced shear force, dominate the environment leading to behavior that we may not observe under terrestrial conditions. Based on these discoveries, the fundamental mechanisms could be better understood and new insights into bioprocesses could be developed for an exciting future.

Antony Jeevarajan↗
NASA NTRSDate not supplied

Extraordinary Accomplishments of the In Space Production Applications Portfolio in 2024

The purpose of the NASA In-Space Production Applications (InSPA) program is to provide funding and expertise to help brilliant United States innovators and businesses traverse the technology “Valley of Death” by proving out their concepts for in-space manufactured materials and products that will ultimately be sold to customers on the Earth. Scientific and technological advances on the International Space Station (ISS) and on Earth coupled with evolving societal needs are collectively enabling InSPA-funded teams to produce data streams and advanced biological, chemical, and physical materials solutions with economic value. We report on an extraordinary year of accomplishments on the ISS and highlight top InSPA and ISS National Lab results that span historic firsts in cancer research, stem cells, crystal production, optical fiber production, drug discovery, in-space treatments with RNA therapeutics, and production of artificial retinas from space. We assert that the results have enormous potential, are transforming the space exploration ecosystem and are the “seeds” of a microgravity industrial revolution that are shaping national microgravity strategy.

in spa↗
NASA NTRSDate not supplied

Microgravity Game Changers: Recent Accomplishments of Microgravity Assisted Materials Experiments on the ISS

This paper discusses important new materials, devices and technology produced in low-Earth orbit (LEO) that have been developed with funding from NASA’s In Space Production Applications (InSPA) Portfolio. In coordination with the International Space Station (ISS) National Laboratory, InSPA supports innovative small businesses and other research & development organizations to develop microgravity-assisted applications that make significant impacts in a wide variety of industries on Earth. These technology development efforts are using the microgravity of orbital space to overcome gravity-induced defects on Earth to create high-value products for terrestrial markets in the areas of semiconductors, pharmaceuticals, and communications. Through 24/7/365 operation on ISS for 25 years, coupled with commercial space transportation and services to, in, and from orbit, the microgravity environment has enabled pioneering science and significant commercial applications, including novel medical advances. World-leading researchers, innovators, and space payload developers provide compelling evidence through demonstrations on the ISS that materials processing in microgravity improves outcomes for a wide range of materials and products at all levels of the organization of matter, from quantum entities such as Bose-Einstein condensates, to crystals, alloys, composites, thin films, and photonics, to stem cells, medical diagnoses, medical treatments, and medical devices for humans. As of 2026, numerous examples proved by demonstration on ISS show the potential of these technologies in various fields. In this paper, a summary of four important experiments is presented.

microgravity medical devices↗
NASA NTRSDate not supplied

CDKN1A/P21’S Role in Osteoprogenitor Fate Regulation in Response to Mechanical Loading: A Single Cell Resolution Investigation

Forces generated by gravity in load-bearing tissues such as bone marrow promote stem cell-based tissue-regenerative processes by increasing proliferation and differentiation of tissue progenitors. Conversely, in microgravity, mouse bone marrow mesenchymal and hematopoietic precursors down-regulate differentiation markers and up-regulate stemness maintenance genes. During microgravity, these transcriptomic changes are associated with Cdkn1a overexpression in osteoprogenitors, and further the homozygous deletion of the CDKN1a gene in the mouse model results in elevated stem-cell based regeneration of severed digits and ear-hole punches. In this work we sought to test the hypothesis that gravity mechanotransduction regulates mesenchymal stem cell derived osteoprogenitor based osteogenesis by modulating proliferation and differentiation fates at specific cell cycle stages via a p21/CDKN1a-regulated mechanism.. To test our hypothesis, we isolated primary mouse bone marrow osteoprogenitors from Cdkn1a-/- (null) or wildtype mice, cultured the cells for 7-days unloaded in osteogenic differentiation media, to allow commitment of the adherent cell population, and subsequently, cultured an additional 48-hours under cyclic stretch or static control loading conditions. After 48-hours of dynamic mechanical loading, we used a 10X Genomics Chromium/Single Cell controller to generate bar-coded single cell Illumina libraries and sequenced expressomes for 6,000 static control and 6,000 cyclic stretch cells for each genotype. Stage-specific single cell analyses show Cdkn1a-/- osteogenic cultures are more differentiated with fewer progenitors, and that cyclic stretch further promotes the conversion of progenitors to osteoblasts in both wildtype and Cdkn1a-/- backgrounds. The proportion of late mineralizing osteoblasts doubled in Cdkn1a-/- cultures, but is not affected by load. Finally, single cell expression of Cdkn1a, in the wildtype cells, is most strongly suppressed by cyclic stretch both in early and late osteoblasts, and minimally in the progenitor population. Collectively, our results support the hypothesis that Cdkn1a constitutively plays a mechano-reversible anti-proliferative role during stem cell-based bone tissue regeneration, and suggests a new molecular target to counter regenerative deficits caused by disuse.

Eduardo Almeida↗
NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Broad tissue degeneration and the failure of normal tissue regenerative processes in microgravity because of mechanical unloading are increasing concerns for sustaining life in space as the duration of future flight missions increases. Work in our laboratory has identified normal adult stem cell-based tissue regenerative processes, such as the formation of new bone, cartilage, and immune cells, as being particularly sensitive to the stresses of mechanical unloading in microgravity. Our studies have also identified the inhibition of differentiation of marrow mesenchymal stem cells and activation of CDKN1ap21-mediated cell cycle arrest in proliferative osteoprecursor cells on the bone surface as potential mechanisms for spaceflight-induced skeletal changes. This finding, in combination with the role of CDKN1ap21 as a suppressor of mammalian tissue regeneration, suggests that this gene could be responsible for suppressing stem cell-based tissue regeneration in response to disuse. In this work, we hypothesized that CDKN1ap21 regulates regenerative bone formation in response to alterations in mechanical load and tested this hypothesis by studying the skeletal phenotype and stem cell regenerative ability of juvenile (4-11 weeks old) and adult (18 weeks-12 months old) p21 (--) knockout (KO) mice. Additionally, we analyzed bone micro-architectural properties, bone formation rates and differentiation capacity of bone marrow stem cells (BMSCs) from male and female KO mice exposed to hindlimb unloading (HU) for 15-30 days. We found that juvenile KO mice exhibited increased femoral trabecular and cortical bone formation, whilst three-point bending of the tibias from KO mice showed decreased bone stiffness. Conversely, adult KO mice exhibited no significant differences in micro-architectural properties compared to WT (wild-type) but woven bone structure was indicative of rapid bone remodeling. Furthermore, cortical bone properties showed similar characteristics to aged bone, including increased cross-sectional area and perimeter, whilst three-point bending showed increased stiffness and toughness. Interestingly, in-vitro, KO mice exhibited increased differentiation and mineralized nodule formation in osteoblastogenesis assays compared to WT. Preliminary results from CDKN1ap21 KO mice subjected to HU suggest altered sensitivity to mechanical unloading resulting in decreased cortical thickness compared to WT mice. However, KO mice subjected to short and long-duration HU show increased in-vitro differentiation potential of BMSCs to from form mature, mineral-forming osteoblasts, indicating maintenance of regenerative potential. Analysis of bone formation rates, cell proliferation rates and key genes of interest are currently underway. These results indicate a novel role for CDKN1ap21 in load-dependent osteoprogenitor proliferation and differentiation and that deletion of CDKN1ap21 results in an age-dependent release of osteoblast proliferation inhibition and increased bone formation and turnover.

Stem Cells↗
NASA NTRS2016

Femoral Head Bone Loss Following Short and Long-Duration Spaceflight

Exposure to mechanical unloading during spaceflight is known to have significant effects on the musculoskeletal system. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. The 30-day BionM1 and the 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight and furthermore would result in significant tissue alterations. MicroCT analysis of BionM1 femurs revealed 31% decrease in bone volume ratio, a 14% decrease in trabecular thickness, and a 20% decrease in trabecular number in the femoral head of space-flown mice. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. However, mice from RR1 exhibited significant bone loss in the femoral head but did not exhibit the severe aging and disease-like phenotype observed during BionM1.This may be due to increased physical activity in the RH hardware. Immunohistochemical analysis of the epiphyseal plate and investigation of cellular proliferation and differentiation pathways within the marrow compartment and whole bone tissue is currently being conducted to determine alterations in stem cell-based tissue regeneration between these experiments. Our results show that the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight femurs from BionM1 indicate onset of an accelerated aging-like phenotype with signs of osteoarthritic disease shown by disruption of the epiphyseal boundary and endochondral ossification. These effects are likely caused by a failure of stem cells to regenerate degraded tissues and may have significant implications for bone and cartilage health following extensive periods of mechanical unloading during long-duration spaceflight.

microgravity↗