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Discoveries from human stem cell research in space that are relevant to advancing cellular therapies on Earth. 从太空人类干细胞研究中发现与推动地球细胞疗法有关的发现。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-21 DOI: 10.1038/s41526-024-00425-0
Fay Ghani, Abba C Zubair

Stem cell research performed in space has provided fundamental insights into stem cell properties and behavior in microgravity including cell proliferation, differentiation, and regeneration capabilities. However, there is broader scientific value to this research including potential translation of stem cell research in space to clinical applications. Here, we present important discoveries from different studies performed in space demonstrating the potential use of human stem cells as well as the limitations in cellular therapeutics. A full understanding of the effects of microgravity in space on potentially supporting the expansion and/or enhancement of stem cell function is required to translate the findings into clinics.

在太空中进行的干细胞研究为了解干细胞在微重力环境下的特性和行为(包括细胞增殖、分化和再生能力)提供了基本见解。不过,这项研究还有更广泛的科学价值,包括将太空干细胞研究转化为临床应用的潜力。在此,我们将介绍在太空中进行的不同研究的重要发现,展示人类干细胞的潜在用途以及细胞疗法的局限性。要将研究成果转化为临床应用,还需要充分了解太空微重力对支持干细胞功能扩展和/或增强的潜在影响。
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引用次数: 0
Author Correction: Hydrogel mechanical properties in altered gravity. 作者更正:改变重力下的水凝胶机械特性。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-21 DOI: 10.1038/s41526-024-00426-z
Vanja Mišković, Immacolata Greco, Christophe Minetti, Francesca Cialdai, Monica Monici, Arianna Gazzi, Jeremiah Marcellino, Yarjan Abdul Samad, Lucia Gemma Delogu, Andrea C Ferrari, Carlo Saverio Iorio
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引用次数: 0
Functional activities essential for space exploration performed in partial gravity during parabolic flight. 在抛物线飞行过程中,在部分重力状态下进行空间探索所必需的功能活动。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-17 DOI: 10.1038/s41526-024-00422-3
Gilles Clément, Timothy R Macaulay, Austin Bollinger, Hannah Weiss, Scott J Wood

Test subjects were assessed in a partial gravity environment during parabolic flight while they performed mission-critical activities that challenged their balance and locomotion. These functional activities included rising from a seated position and walking, jumping down, recovering from falls, and maintaining an upright stance. Twelve volunteers were tested during 10 parabolas that produced 0.25×g, 0.5×g, or 0.75×g, and at 1×g during level flight intervals between parabolas. Additionally, 14 other subjects were tested using identical procedures in a 1×g laboratory setting. Partial gravity altered the performance of settling after standing and navigating around obstacles. As gravity levels decreased, the time required to stand up, settle, walk, and negotiate obstacles, and the number of falls increased. Information obtained from these tests will allow space agencies to assess the vestibular, sensorimotor, and cardiovascular risks associated with different levels of partial gravity.

在抛物线飞行期间,测试对象在部分重力环境中进行了评估,同时他们还进行了对平衡和运动能力提出挑战的关键任务活动。这些功能活动包括从坐姿起立行走、跳下、从跌倒中恢复以及保持直立姿势。在产生 0.25×g、0.5×g 或 0.75×g 的 10 次抛物线过程中,对 12 名志愿者进行了测试;在抛物线之间的平飞间隔期间,对他们进行了 1×g 的测试。此外,还在 1×g 实验室环境中使用相同程序对另外 14 名受试者进行了测试。部分重力改变了站立和绕过障碍物后的沉降性能。随着重力水平的降低,站立、安顿、行走和绕过障碍物所需的时间以及跌倒的次数都有所增加。从这些测试中获得的信息将使太空机构能够评估与不同程度的部分重力相关的前庭、感觉运动和心血管风险。
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引用次数: 0
Simulated microgravity impairs human NK cell cytotoxic activity against space radiation-relevant leukemic cells. 模拟微重力会损害人类 NK 细胞对太空辐射相关白血病细胞的细胞毒活性。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-14 DOI: 10.1038/s41526-024-00424-1
Bradford M Kuhlman, Jonathan H Diaz, Trang Simon, Kimberly D Reeves, Stephen J Walker, Anthony Atala, Graça Almeida-Porada, Christopher D Porada

Natural killer (NK) cells are an important first-line of defense against malignant cells. Because of the potential for increased cancer risk from astronaut exposure to space radiation, we determined whether microgravity present during spaceflight affects the body's defenses against leukemogenesis. Human NK cells were cultured for 48 h under normal gravity and simulated microgravity (sμG), and cytotoxicity against K-562 (CML) and MOLT-4 (T-ALL) cells was measured using standard methodology or under continuous sμG. This brief exposure to sμG markedly reduced NK cytotoxicity against both leukemias, and these deleterious effects were more pronounced in continuous sμG. RNA-seq performed on NK cells from two additional healthy donors provided insight into the mechanism(s) by which sμG reduced cytotoxicity. Given our prior report of space radiation-induced human T-ALL in vivo, the reduced cytotoxicity against MOLT-4 is striking and raises the possibility that μG may increase astronaut risk of leukemogenesis during prolonged missions beyond LEO.

自然杀伤(NK)细胞是抵御恶性细胞的重要第一道防线。由于宇航员暴露在太空辐射中可能会增加患癌风险,我们研究了太空飞行中的微重力是否会影响人体对白血病发生的防御能力。在正常重力和模拟微重力(sμG)条件下培养人类 NK 细胞 48 小时,并使用标准方法或在持续的 sμG 条件下测量其对 K-562(CML)和 MOLT-4(T-ALL)细胞的细胞毒性。这种短暂的 sμG 暴露明显降低了 NK 对这两种白血病的细胞毒性,而且这些有害影响在连续 sμG 条件下更为明显。对另外两名健康供体的 NK 细胞进行的 RNA-seq 分析有助于深入了解 sμG 降低细胞毒性的机制。鉴于我们之前关于太空辐射诱导人体体内 T-ALL 的报告,针对 MOLT-4 的细胞毒性降低令人震惊,并提出了一种可能性,即在低地轨道以外的长期任务中,μG 可能会增加宇航员白血病发生的风险。
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引用次数: 0
Establishing a method for the cryopreservation of viable peripheral blood mononuclear cells in the International Space Station. 建立在国际空间站冷冻保存有活力的外周血单核细胞的方法。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-09 DOI: 10.1038/s41526-024-00423-2
Hiroto Ishii, Rin Endo, Sanae Hamanaka, Nobuyuki Hidaka, Maki Miyauchi, Naho Hagiwara, Takahisa Miyao, Tohru Yamamori, Tatsuya Aiba, Nobuko Akiyama, Taishin Akiyama

The analysis of cells frozen within the International Space Station (ISS) will provide crucial insights into the impact of the space environment on cellular functions and properties. The objective of this study was to develop a method for cryopreserving blood cells under the specific constraints of the ISS. In a ground experiment, mouse blood was directly mixed with a cryoprotectant and gradually frozen at -80 °C. Thawing the frozen blood sample resulted in the successful recovery of viable mononuclear cells when using a mixed solution of dimethylsulfoxide and hydroxyethyl starch as a cryoprotectant. In addition, we developed new freezing cases to minimize storage space utilization within the ISS freezer. Finally, we confirmed the recovery of major mononuclear immune cell subsets from the cryopreserved blood cells through a high dimensional analysis of flow cytometric data using 13 cell surface markers. Consequently, this ground study lays the foundation for the cryopreservation of viable blood cells on the ISS, enabling their analysis upon return to Earth. The application of this method in ISS studies will contribute to understanding the impact of space environments on human cells. Moreover, this method may find application in the cryopreservation of blood cells in situations where research facilities are inadequate.

对在国际空间站(ISS)内冷冻的细胞进行分析,将有助于深入了解空间环境对细胞功能和特性的影响。这项研究的目的是开发一种在国际空间站特定限制条件下冷冻保存血细胞的方法。在地面实验中,小鼠血液直接与低温保护剂混合,并在零下 80 摄氏度逐渐冷冻。当使用二甲基亚砜和羟乙基淀粉的混合溶液作为低温保护剂时,解冻冷冻血样可成功回收有活力的单核细胞。此外,我们还开发了新的冷冻箱,以最大限度地减少国际空间站冷冻箱的存储空间利用率。最后,我们通过使用 13 种细胞表面标记物对流式细胞数据进行高维分析,证实了从冷冻保存的血细胞中恢复了主要的单核免疫细胞亚群。因此,这项地面研究为在国际空间站上冷冻保存有活力的血细胞奠定了基础,使其能够在返回地球后进行分析。在国际空间站研究中应用这种方法将有助于了解空间环境对人体细胞的影响。此外,这种方法还可用于在研究设施不足的情况下冷冻保存血细胞。
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引用次数: 0
Hydrogel mechanical properties in altered gravity. 改变重力条件下的水凝胶机械特性。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-08 DOI: 10.1038/s41526-024-00388-2
Vanja Mišković, Immacolata Greco, Christophe Minetti, Francesca Cialdai, Monica Monici, Arianna Gazzi, Jeremiah Marcellino, Yarjan Abdul Samad, Lucia Gemma Delogu, Andrea C Ferrari, Carlo Saverio Iorio

Exposure to altered gravity influences cellular behaviour in cell cultures. Hydrogels are amongst the most common materials used to produce tissue-engineering scaffolds, and their mechanical properties play a crucial role in cell-matrix interaction. However, little is known about the influence of altered gravity on hydrogel properties. Here we study the mechanical properties of Poly (ethylene glycol) diacrylate (PEGDA) and PEGDA incorporated with graphene oxide (GO) by performing tensile tests in micro and hypergravity during a Parabolic flight campaign, and by comparing them to the same tests performed in Earth gravity. We show that gravity levels do not result in a statistically significant difference in Young's modulus.

暴露于改变的重力环境会影响细胞培养物中的细胞行为。水凝胶是制造组织工程支架最常用的材料之一,其机械特性在细胞与基质的相互作用中起着至关重要的作用。然而,人们对重力改变对水凝胶特性的影响知之甚少。在这里,我们研究了聚(乙二醇)二丙烯酸酯(PEGDA)和聚(乙二醇)二丙烯酸酯与氧化石墨烯(GO)结合的机械性能,方法是在抛物线飞行活动中进行微重力和超重力拉伸测试,并将它们与在地球重力下进行的相同测试进行比较。结果表明,重力水平不会导致杨氏模量出现统计学上的显著差异。
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引用次数: 0
Light has a principal role in the Arabidopsis transcriptomic response to the spaceflight environment. 光在拟南芥转录组对太空飞行环境的反应中起着主要作用。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-08-06 DOI: 10.1038/s41526-024-00417-0
Mingqi Zhou, Robert J Ferl, Anna-Lisa Paul

The Characterizing Arabidopsis Root Attractions (CARA) spaceflight experiment provides comparative transcriptome analyses of plants grown in both light and dark conditions within the same spaceflight. CARA compared three genotypes of Arabidopsis grown in ambient light and in the dark on board the International Space Station (ISS); Col-0, Ws, and phyD, a phytochrome D mutant in the Col-0 background. In all genotypes, leaves responded to spaceflight with a higher number of differentially expressed genes (DEGs) than root tips, and each genotype displayed distinct light / dark transcriptomic patterns that were unique to the spaceflight environment. The Col-0 leaves exhibited a substantial dichotomy, with ten-times as many spaceflight DEGs exhibited in light-grown plants versus dark-grown plants. Although the total number of DEGs in phyD leaves is not very different from Col-0, phyD altered the manner in which light-grown leaves respond to spaceflight, and many genes associated with the physiological adaptation of Col-0 to spaceflight were not represented. This result is in contrast to root tips, where a previous CARA study showed that phyD substantially reduced the number of DEGs. There were few DEGs, but a series of space-altered gene categories, common to genotypes and lighting conditions. This commonality indicates that key spaceflight genes are associated with signal transduction for light, defense, and oxidative stress responses. However, these key signaling pathways enriched from DEGs showed opposite regulatory direction in response to spaceflight under light and dark conditions, suggesting a complex interaction between light as a signal, and light-signaling genes in acclimation to spaceflight.

拟南芥根吸引特性(CARA)太空飞行实验对同一太空飞行期间在光照和黑暗条件下生长的植物进行了转录组比较分析。CARA 比较了在国际空间站(ISS)上环境光和黑暗条件下生长的三种拟南芥基因型:Col-0、Ws 和 phyD(Col-0 背景下的植物色素 D 突变体)。在所有基因型中,叶片对太空飞行的反应比根尖有更多的差异表达基因(DEG),而且每个基因型都显示出太空飞行环境所特有的独特的光/暗转录组模式。Col-0叶片表现出明显的二分法,光照生长植株的太空飞行 DEGs 数量是黑暗生长植株的十倍。虽然 phyD 叶片中 DEGs 的总数与 Col-0 没有太大差别,但 phyD 改变了光照生长叶片对太空飞行的反应方式,许多与 Col-0 对太空飞行的生理适应有关的基因没有出现。这一结果与根尖形成了鲜明对比,之前的一项 CARA 研究表明,phyD 大大减少了根尖 DEGs 的数量。DEGs的数量很少,但有一系列空间改变的基因类别,这些基因类别在基因型和光照条件下都很常见。这种共性表明,关键的太空飞行基因与光照、防御和氧化应激反应的信号转导有关。然而,从 DEGs 中富集的这些关键信号通路在光照和黑暗条件下的太空飞行反应中显示出相反的调控方向,这表明在适应太空飞行过程中,光作为一种信号与光信号基因之间存在着复杂的相互作用。
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引用次数: 0
Rotational and translational motions in a homogeneously cooling granular gas. 均匀冷却颗粒气体中的旋转和平移运动。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-07-31 DOI: 10.1038/s41526-024-00420-5
Torsten Trittel, Dmitry Puzyrev, Kirsten Harth, Ralf Stannarius

A granular gas composed of monodisperse spherical particles was studied in microgravity experiments in a drop tower. Translations and rotations of the particles were extracted from optical video data. Equipartition is violated, the rotational degrees of freedom were excited only to roughly 2/3 of the translational ones. After stopping the mechanical excitation, we observed granular cooling of the ensemble for a period of three times the Haff time, where the kinetic energy dropped to about 5% of its initial value. The cooling rates of all observable degrees of freedom were comparable, and the ratio of rotational and translational kinetic energies fluctuated around a constant value. The distributions of translational and rotational velocity components showed slight but systematic deviations from Gaussians at the start of cooling.

在落塔的微重力实验中研究了由单分散球形颗粒组成的颗粒气体。粒子的平移和旋转是从光学视频数据中提取的。由于违反了等分原则,旋转自由度仅被激发到平移自由度的大约 2/3。停止机械激励后,我们观察到粒子群在三倍哈夫时间内出现颗粒状冷却,动能下降到初始值的大约 5%。所有可观测自由度的冷却速率相当,旋转动能和平移动能之比围绕一个恒定值波动。在冷却开始时,平移和旋转速度分量的分布与高斯分布有轻微但系统的偏差。
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引用次数: 0
Growth and mineralization of fetal mouse long bones under microgravity and daily 1 g gravity exposure. 胎鼠长骨在微重力和每日 1 克重力暴露下的生长和矿化。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-07-27 DOI: 10.1038/s41526-024-00421-4
Jack J W A van Loon, Olga P Berezovska, Theodorus J M Bervoets, Dina Montufar-Solis, Cor M Semeins, Behrouz Zandieh-Doulabi, P Natalia V Rodionova, Jackie Duke, J Paul Veldhuijzen

In a previous Space Shuttle/Spacelab experiment (STS-42), we observed direct responses of isolated fetal mouse long bones to near weightlessness. This paper aimed to verify those results and study the effects of daily 1×g exposure during microgravity on the growth and mineralization of these bones. Two experiments were conducted: one on an American Space Shuttle mission (IML-2 on STS-65) and another on a Russian Bio-Cosmos flight (Bion-10 on Cosmos-2229). Despite differences in hardware, both used 17-day-old fetal mouse metatarsals cultured for 4 days. Results showed reduced proteoglycan content under microgravity compared to 1×g conditions, with no main differences in other cellular structures. While the overall metatarsal length was unaffected, the length increase of the mineralized diaphysis was significantly reduced under microgravity. Daily 1×g exposure for at least 6 h abolished the microgravity-induced reduction in cartilage mineralization, indicating the need for long-duration exposure to 1×g as an in-flight countermeasure using artificial gravity.

在之前的航天飞机/太空实验室实验(STS-42)中,我们观察到离体胎鼠长骨对近乎失重状态的直接反应。本文旨在验证这些结果,并研究在微重力状态下每天暴露于 1×g 的环境对这些骨骼的生长和矿化的影响。我们进行了两项实验:一项在美国航天飞机飞行任务(STS-65 上的 IML-2)中进行,另一项在俄罗斯生物宇宙飞行任务(Cosmos-2229 上的 Bion-10)中进行。尽管硬件不同,但都使用了培养 4 天的 17 天大的胎鼠跖骨。结果显示,与 1×g 条件相比,微重力条件下蛋白多糖含量减少,其他细胞结构没有主要差异。虽然跖骨的整体长度未受影响,但矿化干骺端的长度增长在微重力条件下明显减少。每天暴露于1×g条件下至少6小时可消除微重力引起的软骨矿化减少,这表明需要长时间暴露于1×g条件下,作为利用人工重力的飞行中对策。
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引用次数: 0
Advancing insights into microgravity induced muscle changes using Caenorhabditis elegans as a model organism. 以秀丽隐杆线虫为模式生物,推进对微重力诱发的肌肉变化的深入研究。
IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-07-26 DOI: 10.1038/s41526-024-00418-z
Laura J Beckett, Philip M Williams, Li Shean Toh, Volker Hessel, Lukas Gerstweiler, Ian Fisk, Luis Toronjo-Urquiza, Veeren M Chauhan

Spaceflight presents significant challenges to the physiological state of living organisms. This can be due to the microgravity environment experienced during long-term space missions, resulting in alterations in muscle structure and function, such as atrophy. However, a comprehensive understanding of the adaptive mechanisms of biological systems is required to devise potential solutions and therapeutic approaches for adapting to spaceflight conditions. This review examines the current understanding of the challenges posed by spaceflight on physiological changes, alterations in metabolism, dysregulation of pathways and the suitability and advantages of using the model organism Caenorhabditis elegans nematodes to study the effects of spaceflight. Research has shown that changes in the gene and protein composition of nematodes significantly occur across various larval stages and rearing environments, including both microgravity and Earth gravity settings, often mirroring changes observed in astronauts. Additionally, the review explores significant insights into the fundamental metabolic changes associated with muscle atrophy and growth, which could lead to the development of diagnostic biomarkers and innovative techniques to prevent and counteract muscle atrophy. These insights not only advance our understanding of microgravity-induced muscle atrophy but also lay the groundwork for the development of targeted interventions to mitigate its effects in the future.

太空飞行对生物体的生理状态提出了重大挑战。这可能是由于长期太空任务中经历的微重力环境,导致肌肉结构和功能发生变化,如萎缩。然而,需要全面了解生物系统的适应机制,才能设计出适应太空飞行条件的潜在解决方案和治疗方法。本综述探讨了目前对太空飞行对生理变化、新陈代谢改变、途径失调所构成挑战的理解,以及利用模式生物秀丽隐杆线虫研究太空飞行影响的适宜性和优势。研究表明,线虫的基因和蛋白质组成在不同的幼虫阶段和饲养环境(包括微重力和地球重力环境)中都会发生显著变化,这些变化往往与在宇航员身上观察到的变化相同。此外,该综述还探讨了与肌肉萎缩和生长相关的基本代谢变化的重要见解,这可能会导致诊断生物标志物和创新技术的开发,以防止和抵消肌肉萎缩。这些见解不仅增进了我们对微重力诱发肌肉萎缩的了解,还为今后开发有针对性的干预措施以减轻其影响奠定了基础。
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引用次数: 0
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