利用人类多能干细胞模拟神经心脏生理学和疾病:当前进展与未来展望
Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.
作者信息
Wu Hsueh-Fu, Hamilton Charlotte, Porritt Harrison, Winbo Annika, Zeltner Nadja
机构信息
Center for Molecular Medicine, University of Georgia, Athens, Georgia, USA.
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA.
出版信息
J Physiol. 2025 Mar;603(7):1865-1885. doi: 10.1113/JP286416. Epub 2024 Sep 5.
Throughout our lifetime the heart executes cycles of contraction and relaxation to meet the body's ever-changing metabolic needs. This vital function is continuously regulated by the autonomic nervous system. Cardiovascular dysfunction and autonomic dysregulation are also closely associated; however, the degrees of cause and effect are not always readily discernible. Thus, to better understand cardiovascular disorders, it is crucial to develop model systems that can be used to study the neurocardiac interaction in healthy and diseased states. Human pluripotent stem cell (hiPSC) technology offers a unique human-based modelling system that allows for studies of disease effects on the cells of the heart and autonomic neurons as well as of their interaction. In this review, we summarize current understanding of the embryonic development of the autonomic, cardiac and neurocardiac systems, their regulation, as well as recent progress of in vitro modelling systems based on hiPSCs. We further discuss the advantages and limitations of hiPSC-based models in neurocardiac research.
在我们的一生中,心脏执行收缩和舒张周期以满足身体不断变化的代谢需求。这一重要功能由自主神经系统持续调节。心血管功能障碍与自主神经调节异常也密切相关;然而,因果关系的程度并不总是容易辨别。因此,为了更好地理解心血管疾病,开发可用于研究健康和患病状态下神经心脏相互作用的模型系统至关重要。人类多能干细胞(hiPSC)技术提供了一个独特的基于人类的建模系统,可用于研究疾病对心脏细胞和自主神经元及其相互作用的影响。在这篇综述中,我们总结了目前对自主神经系统、心脏系统和神经心脏系统胚胎发育、它们的调节以及基于hiPSC的体外建模系统的最新进展的理解。我们还讨论了基于hiPSC的模型在神经心脏研究中的优点和局限性。