ISS/Collaborative Research: Studying the Effects of Microgravity on 3D Cardiac Organoid Cultures

众所周知，在航天飞行期间暴露在微重力下会导致心脏萎缩，这是心脏组织质量的减少，导致心脏功能的衰弱变化。患有癌症和其他疾病的患者也会出现心脏萎缩，这些疾病包括肌肉营养不良、糖尿病、败血症和心力衰竭。由于心肌萎缩尚未得到很好的了解，本项目旨在提高对心肌萎缩进展过程中细胞和组织功能的基本了解。进行这项研究的是一个跨学科和多机构的团队，由生物医学工程师和科学家组成，他们在心脏组织生物打印以及细胞和分子生物学方面拥有互补的专业知识。利用国际空间站(ISS)的微重力环境来诱导萎缩，研究小组将使用生物打印的心脏组织来研究组织功能的变化。所获得的知识将支持对心脏萎缩如何以及为什么发生的更好的理解，这可能导致改进的治疗策略。该项目还将为国际空间站上的K12学生开发一个围绕组织工程的研讨会，并为医学生、实习生和居民举办一次研讨会，讨论将研究从地面实验室转移到太空的好处和挑战。首先，比较和对比3D生物打印心脏器官在微重力和地球重力下的形态、活性和改变的能量代谢。第二，研究微重力下3D生物打印心脏器官的表观遗传学变化，并评估与地球重力相比，这些变化可能如何影响心脏萎缩的发展。具体地说，该团队将设计并验证一种用于培养心肌细胞、成纤维细胞和内皮细胞的芯片设计，以调查在微重力暴露期间对细胞造成损害的潜在生物和信号介质，从而可能导致心脏萎缩。研究结果可能表明，表观遗传事件可能是微重力引起的心脏萎缩相关基因表达变化的机制基础之一，并可能有助于开发对策，以防止微重力或其他导致心肌萎缩的病理学的不利影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Exposure to microgravity during spaceflight is known to lead to cardiac atrophy, which is a reduction in tissue mass of the heart that causes debilitating changes in heart function. Cardiac atrophy can also present itself in patients suffering from cancer and other diseases, including muscular dystrophies, diabetes, sepsis and heart failure. Because cardiac atrophy is not well understood, this project seeks to improve fundamental understanding of cell and tissue function during progression of cardiac atrophy. Undertaking this research is an interdisciplinary and multi-institutional team comprised of biomedical engineers and scientists with complementary expertise in cardiac tissue bioprinting and cellular and molecular biology. Using the micro-gravity environment of the International Space Station (ISS) to induce atrophy, the team will use bioprinted heart tissue to study changes in tissue function. The knowledge gained will support an improved understanding of how and why cardiac atrophy occurs, which may lead to improved treatment strategies. The project will also develop a workshop for K12 students around tissue engineering on the international space station as well as implement a seminar for medical students, interns, and residents about the benefits and challenges of transitioning research from an Earth-based laboratory into space.Two objectives have been established for this project. First, to compare and contrast the morphology, viability, and altered energy metabolism in 3D bioprinted cardiac organoids under microgravity and Earth's gravity. Second, to study the epigenetic changes in 3D bioprinted cardiac organoids under microgravity and assess how these changes may affect the development of cardiac atrophy when compared to Earth's gravity. Specifically, the team will engineer and validate a chip design for culturing of cardiomyocytes, fibroblasts and endothelial cells to investigate underlying biological and signaling mediators responsible for damage to cells during microgravity exposure, leading to possible cardiac atrophy. Findings may suggest that epigenetic events could be one of the mechanistic bases for microgravity‐induced gene expression changes related to cardiac atrophy and may facilitate the development of countermeasures to prevent the adverse effects of microgravity or other atrophy-inducing pathologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.