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于微重力会导致心脏萎缩，这是心脏组织质量的减少，导致心脏功能的衰弱性变化。心脏萎缩也可以出现在患有癌症和其他疾病的患者中，包括肌肉萎缩症、糖尿病、败血症和心力衰竭。由于对心脏萎缩的了解还不充分，本项目旨在提高对心脏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和细胞和分子生物学方面具有互补的专业知识。利用国际空间站（ISS）的微重力环境来诱导萎缩，该团队将使用生物打印的心脏组织来研究组织功能的变化。 所获得的知识将有助于更好地了解心脏萎缩是如何发生的，以及为什么会发生，这可能会导致改善治疗策略。 该项目还将为K12学生在国际空间站上组织工程开发一个研讨会，并为医学生、实习生和居民举办一个研讨会，讨论将研究从地球实验室转移到太空的好处和挑战。 首先，比较和对比微重力和地球重力下3D生物打印心脏类器官的形态，活力和改变的能量代谢。 其次，研究微重力下3D生物打印心脏类器官的表观遗传变化，并评估与地球重力相比，这些变化如何影响心脏萎缩的发展。 具体来说，该团队将设计和验证用于培养心肌细胞，成纤维细胞和内皮细胞的芯片设计，以研究在微重力暴露期间导致细胞损伤的潜在生物和信号传导介质，从而导致可能的心脏萎缩。研究结果可能表明，表观遗传事件可能是微重力的机械基础之一‐该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.