Simulated microgravity improves maturation of cardiomyocytes derived from human induced pluripotent stem cells.
Simulated microgravity improves maturation of cardiomyocytes derived from human induced pluripotent stem cells.
复制标题
DOI：
10.1038/s41598-024-52453-1
复制
发表时间：
2024-01-26
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
源自人类诱导多能干细胞（hiPSC-CM）的心肌细胞具有基础研究和转化应用的巨大潜力。然而，这些细胞在结构和功能上类似于胎儿心肌细胞，这是这些细胞的主要限制。微重力可以显着改变细胞的行为和功能。在这里，我们研究了模拟微重力对 hiPSC-CM 成熟的影响。在随机定位机中模拟微重力下培养 7 天后，通过线粒体蛋白和线粒体 DNA 与核 DNA 的比率检测到，3D hiPSC-CM 的线粒体含量有所增加。这些细胞的线粒体膜电位也增加。一致地，模拟微重力增加了 3D hiPSC-CM 中的线粒体呼吸，如最高水平的最大呼吸和 ATP 含量所示，这表明与正常重力下的培养物相比，模拟微重力培养物中的代谢成熟得到改善。来自模拟微重力培养物的细胞还具有改善的 Ca2+ 瞬态参数，这是更成熟的心肌细胞的功能特征。此外，这些细胞具有与更成熟的心肌细胞相关的改善的结构特性，包括增加的肌节长度、z盘长度、核直径和核偏心率。这些发现表明微重力促进 hiPSC-CM 在结构、代谢和功能水平上的成熟。
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous potential for basic research and translational application. However, these cells structurally and functionally resemble fetal cardiomyocytes, which is a major limitation of these cells. Microgravity can significantly alter cell behavior and function. Here we investigated the effect of simulated microgravity on hiPSC-CM maturation. Following culture under simulated microgravity in a random positioning machine for 7 days, 3D hiPSC-CMs had increased mitochondrial content as detected by a mitochondrial protein and mitochondrial DNA to nuclear DNA ratio. The cells also had increased mitochondrial membrane potential. Consistently, simulated microgravity increased mitochondrial respiration in 3D hiPSC-CMs, as indicated by higher levels of maximal respiration and ATP content, suggesting improved metabolic maturation in simulated microgravity cultures compared with cultures under normal gravity. Cells from simulated microgravity cultures also had improved Ca2+ transient parameters, a functional characteristic of more mature cardiomyocytes. In addition, these cells had improved structural properties associated with more mature cardiomyocytes, including increased sarcomere length, z-disc length, nuclear diameter, and nuclear eccentricity. These findings indicate that microgravity enhances the maturation of hiPSC-CMs at the structural, metabolic, and functional levels.
登录
查看更多内容
影响因子：
16.6
作者：
Funakoshi S;Fernandes I;Mastikhina O;Wilkinson D;Tran T;Dhahri W;Mazine A;Yang D;Burnett B;Lee J;Protze S;Bader GD;Nunes SS;Laflamme M;Keller G
通讯作者：
Keller G
影响因子：
20.1
作者：
Hu D;Linders A;Yamak A;Correia C;Kijlstra JD;Garakani A;Xiao L;Milan DJ;van der Meer P;Serra M;Alves PM;Domian IJ
通讯作者：
Domian IJ
影响因子：
4.6
作者：
Jha R;Wu Q;Singh M;Preininger MK;Han P;Ding G;Cho HC;Jo H;Maher KO;Wagner MB;Xu C
通讯作者：
Xu C
影响因子：
20.1
作者：
Campostrini G;Windt LM;van Meer BJ;Bellin M;Mummery CL
通讯作者：
Mummery CL
影响因子：
3.3
作者：
Connor, MK;Hood, DA
通讯作者：
Hood, DA