Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA.
Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.
Biomaterials. 2023 Oct;301:122267. doi: 10.1016/j.biomaterials.2023.122267. Epub 2023 Aug 11.
Cosmic radiation is the most serious risk that will be encountered during the planned missions to the Moon and Mars. There is a compelling need to understand the effects, safety thresholds, and mechanisms of radiation damage in human tissues, in order to develop measures for radiation protection during extended space travel. As animal models fail to recapitulate the molecular changes in astronauts, engineered human tissues and "organs-on-chips" are valuable tools for studying effects of radiation in vitro. We have developed a bioengineered tissue platform for studying radiation damage in individualized settings. To demonstrate its utility, we determined the effects of radiation using engineered models of two human tissues known to be radiosensitive: engineered cardiac tissues (eCT, a target of chronic radiation damage) and engineered bone marrow (eBM, a target of acute radiation damage). We report the effects of high-dose neutrons, a proxy for simulated galactic cosmic rays, on the expression of key genes implicated in tissue responses to ionizing radiation, phenotypic and functional changes in both tissues, and proof-of-principle application of radioprotective agents. We further determined the extent of inflammatory, oxidative stress, and matrix remodeling gene expression changes, and found that these changes were associated with an early hypertrophic phenotype in eCT and myeloid skewing in eBM. We propose that individualized models of human tissues have potential to provide insights into the effects and mechanisms of radiation during deep-space missions and allow testing of radioprotective measures.
宇宙辐射是在计划中的月球和火星任务中最严重的风险。为了开发延长太空旅行期间的辐射防护措施,迫切需要了解人类组织中辐射损伤的影响、安全阈值和机制。由于动物模型未能重现宇航员的分子变化,因此工程化的人体组织和“芯片上器官”是体外研究辐射影响的有价值工具。我们已经开发了一种用于研究个体化设置中辐射损伤的生物工程组织平台。为了证明其效用,我们使用两种已知对辐射敏感的工程化人体组织模型(工程化心脏组织(eCT,慢性辐射损伤的靶标)和工程化骨髓(eBM,急性辐射损伤的靶标))确定了辐射的影响。我们报告了高剂量中子(模拟银河宇宙射线的替代物)对涉及组织对电离辐射反应的关键基因表达、两种组织的表型和功能变化的影响,以及放射防护剂的原理验证应用。我们进一步确定了炎症、氧化应激和基质重塑基因表达变化的程度,并发现这些变化与 eCT 中的早期肥大表型和 eBM 中的骨髓细胞向髓系分化有关。我们提出,个体化的人体组织模型有可能深入了解深空任务期间辐射的影响和机制,并允许测试放射防护措施。