Lopez Andrew L, Wang Shang, Larina Irina V
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey, USA.
J Biophotonics. 2020 Nov;13(11):e202000223. doi: 10.1002/jbio.202000223. Epub 2020 Aug 18.
The mouse embryo is an established model for investigation of regulatory mechanisms controlling cardiac development and congenital heart defects in humans. Since cultured mouse embryos are very sensitive to any manipulations and environmental fluctuations, controlled alterations in mouse embryonic cardiac function are extremely challenging, which is a major hurdle in mammalian cardiac biomechanics research. This manuscript presents first optogenetic manipulation of cardiodynamics and hemodynamics in cultured mouse embryos. Optogenetic pacing was combined with 4D (3D + time) optical coherence tomography structural and Doppler imaging, demonstrating that embryonic hearts under optogenetic pacing can function efficiently and produce strong blood flows. This study demonstrates that the presented method is a powerful tool giving quick, consistent, reversible control over heart dynamics and blood flow under real time visualization, enabling various live cardiac biomechanics studies toward better understanding of normal cardiogenesis and congenital heart defects in humans.
小鼠胚胎是研究控制人类心脏发育和先天性心脏缺陷的调节机制的成熟模型。由于培养的小鼠胚胎对任何操作和环境波动都非常敏感,因此对小鼠胚胎心脏功能进行可控改变极具挑战性,这是哺乳动物心脏生物力学研究中的一个主要障碍。本手稿首次展示了对培养的小鼠胚胎进行心脏动力学和血流动力学的光遗传学操作。光遗传学起搏与4D(3D + 时间)光学相干断层扫描结构和多普勒成像相结合,表明光遗传学起搏下的胚胎心脏能够高效运作并产生强劲的血流。这项研究表明,所提出的方法是一种强大的工具,能够在实时可视化的情况下对心脏动力学和血流进行快速、一致、可逆的控制,从而开展各种活体心脏生物力学研究,以更好地了解人类正常心脏发生和先天性心脏缺陷。