Forghani Parvin, Liu Wenhao, Wang Zeyu, Ling Zhi, Takaesu Felipe, Yang Evan, Tharp Gregory K, Nielsen Sheila, Doraisingam Shankini, Countryman Stefanie, Davis Michael E, Wu Ronghu, Jia Shu, Xu Chunhui
Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Biomaterials. 2025 Jun;317:123080. doi: 10.1016/j.biomaterials.2024.123080. Epub 2025 Jan 6.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs. Cardiac spheroids derived from hiPSCs were transported to the International Space Station (ISS) via the SpaceX Crew-8 mission and cultured under space microgravity for 8 days. Beating cardiac spheroids were observed on the ISS and upon successful experimentation by the astronauts in space, the live cultures were returned to Earth. These cells had normal displacement (an indicator of contraction) and Ca transient parameters in 3D live cell imaging. Proteomic analysis revealed that spaceflight upregulated many proteins involved in metabolism (n = 90), cellular component of mitochondrion (n = 62) and regulation of proliferation (n = 10). Specific metabolic pathways enriched by spaceflight included glutathione metabolism, biosynthesis of amino acids, and pyruvate metabolism. In addition, the top upregulated proteins in spaceflight samples included those involved in cellular stress response, cell survival, and metabolism. Transcriptomic profiles indicated that spaceflight upregulated genes associated with cardiomyocyte development, and cellular components of cardiac structure and mitochondrion. Furthermore, spaceflight upregulated genes in metabolic pathways associated with cell survival such as glycerophospholipid metabolism and glycerolipid metabolism. These findings indicate that short-term exposure of 3D hiPSC-CMs to the space environment led to significant changes in protein levels and gene expression involved in cell survival and metabolism.
源自人类诱导多能干细胞的心肌细胞（hiPSC-CMs）在心脏再生方面具有巨大优势。然而，细胞移植后的细胞存活具有挑战性。由于微重力会深刻影响细胞特性，我们研究了太空飞行对hiPSC-CMs的影响。源自hiPSC的心脏球体通过SpaceX Crew-8任务被运送到国际空间站（ISS），并在太空微重力下培养8天。在国际空间站上观察到跳动的心脏球体，并且在宇航员在太空中成功进行实验后，活培养物被带回地球。这些细胞在3D活细胞成像中具有正常的位移（收缩指标）和钙瞬变参数。蛋白质组学分析表明，太空飞行上调了许多参与代谢的蛋白质（n = 90）、线粒体的细胞成分（n = 62）和增殖调节（n = 10）。太空飞行富集的特定代谢途径包括谷胱甘肽代谢、氨基酸生物合成和丙酮酸代谢。此外，太空飞行样本中上调的顶级蛋白质包括那些参与细胞应激反应、细胞存活和代谢的蛋白质。转录组图谱表明，太空飞行上调了与心肌细胞发育、心脏结构和线粒体的细胞成分相关的基因。此外，太空飞行上调了与细胞存活相关的代谢途径中的基因，如甘油磷脂代谢和甘油脂代谢。这些发现表明，3D hiPSC-CMs短期暴露于太空环境会导致细胞存活和代谢相关的蛋白质水平和基因表达发生显著变化。
