1 Tissue Engineering Research Center, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.
2 Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai, China.
Stem Cells Dev. 2019 Mar 15;28(6):357-360. doi: 10.1089/scd.2018.0240. Epub 2019 Feb 25.
During space travel, exposure to microgravity may have profound influence on the physiological function of mammalian cells. In this study, we took opportunity of the Tianzhou-1 (TZ-1) mission to investigate how spaceflight may affect cardiac differentiation of mouse induced pluripotent stem cells (iPSCs). A bioreactor was engineered to perform cell culturing and the time-lapse imaging experiments on-orbit. Transgenic iPSC lines with either Oct4 or α-myosin heavy chain (αMHC) promoter driving green fluorescent protein (GFP) expression were used to study cardiomyocyte (CM) differentiation in real microgravity. The differentiation status was monitored by GFP fluorescence intensity. Interestingly, compared with cells cultured in identical environment at ground gravity, embryoid bodies (EBs) derived from Oct4 reporter iPSC downregulated GFP significantly quicker in space. Meanwhile, EBs derived from αMHC reporter iPSC activated GFP strongly 4 days after launch (P < 0.05) and lasted for 10 days afterward, indicating robust CM formation. This is the first real-time imaging study of iPSC myocardial differentiation in space. Under our experimental condition, real microgravity enhanced the CM differentiation process of iPSCs. Our study provided rare information about iPSC cardiac differentiation in space. In the future, similar automated stem cell experiments may help to realize personalized cardiac tissue biomanufacturing and drug test during space travel.
在太空旅行中，微重力的暴露可能对哺乳动物细胞的生理功能产生深远影响。在这项研究中，我们利用天舟一号（TZ-1）任务，研究太空飞行如何影响小鼠诱导多能干细胞（iPSC）的心脏分化。我们设计了一个生物反应器，用于在轨道上进行细胞培养和延时成像实验。使用带有 Oct4 或 α-肌球蛋白重链（αMHC）启动子驱动绿色荧光蛋白（GFP）表达的转基因 iPSC 系来研究真实微重力下的心肌细胞（CM）分化。通过 GFP 荧光强度监测分化状态。有趣的是，与在地面重力相同环境中培养的细胞相比，Oct4 报告基因 iPSC 来源的胚状体（EBs）在太空中 GFP 下调明显更快。同时，αMHC 报告基因 iPSC 来源的 EBs 在发射后 4 天（P<0.05）强烈激活 GFP，持续 10 天，表明形成了强大的 CM。这是在太空中对 iPSC 心肌分化进行实时成像研究的首次尝试。在我们的实验条件下，真实微重力增强了 iPSC 的 CM 分化过程。我们的研究为太空 iPSC 心脏分化提供了罕见的信息。在未来，类似的自动化干细胞实验可能有助于实现太空旅行期间的个性化心脏组织生物制造和药物测试。
