干细胞衍生的心肌细胞异质性混了电生理学的见解
Alexander P Clark1, Trine Krogh-Madsen2,3, David J Christini1,4
1Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
The Journal of physiology
|May 9, 2024
概括
人类诱导的多能干细胞衍生心肌细胞 (iPSC-CMs) 对药物测试有希望,但表现出显著的电生理学异质性. 这种由实验方法加剧的变异性阻碍了准确的患者特异性心血管疾病建模.
科学领域:
- 心脏病学 心脏病学
- 干细胞生物学 干细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类诱导的多能干细胞衍生心肌细胞 (iPSC-CMs) 是药物心脏毒性和个性化心血管疾病研究的宝贵体外模型.
- 目前,iPSC-CMs之间的电生理学异质性限制了实验洞察力和翻译潜力的深度.
- 了解和缓解这种异质性对于推进iPSC-CM应用至关重要.
研究的目的:
- 审查iPSC-CM中电生理学异质性的来源和后果.
- 要突出实验文物,特别是来自补丁技术的实验文物,如何加剧这种异质性.
- 讨论iPSC-CM异质性对患者衍生心肌细胞数字双胞胎的发展的影响.
主要方法:
- 文献综述和对现有关于iPSC-CM电生理学的研究进行批判性分析.
- 检查实验方法,专注于补丁技术 (手动和自动化).
- 讨论导致细胞变化的内在和外在因素.
主要成果:
- 在iPSC-CM文献中普遍存在显著的电生理学异质性.
- 在手动和自动设置中,补丁器器件明显恶化了iPSC-CM异质性.
- 内在的细胞特性和外在的实验条件都对观察到的变异性有所贡献.
结论:
- 电生理学异质性是iPSC-CMs的一个主要挑战,影响了它们作为体外模型的实用性.
- 实验协议的标准化和文物减轻对于提高iPSC-CM可靠性至关重要.
- 解决异质性对于成功开发心血管研究患者特定的数字双胞胎模型至关重要.
更多相关视频
09:05In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
10.9K
08:06Generation of Ventricular-Like HiPSC-Derived Cardiomyocytes and High-Quality Cell Preparations for Calcium Handling Characterization
Published on: January 17, 2020
7.9K
相关概念视频
Electromagnetic Fields
Electric fields generated by static charges, often referred to as electrostatic fields, are characteristically different from electric fields created by time-varying magnetic fields. While the former is a conservative field, implying that no net work is done on a test charge if it goes around in a complete loop in the field, the latter is, by definition, not a conservative field; net work is done, and it is proportional to the rate of change of magnetic flux.
However, the observation of Gauss's...
However, the observation of Gauss's...
Structure of Cardiac Muscles
Cardiac muscle, or myocardium, is a specialized type of muscle found exclusively in the heart. Its unique structural and functional characteristics enable the heart to perform its vital role of pumping blood throughout the body continuously and rhythmically. The cardiac muscle cells, or cardiomyocytes, possess an endomysium and perimysium but do not have an epimysium.
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
Specialized Characteristics of Cardiac Muscles
The primary role of cardiac muscles is to propel blood throughout the cardiovascular system. The cardiac muscle cells, or cardiomyocytes, exhibit specialized characteristics that allow them to perform this function.
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
Electrophysiology of Normal Cardiac Rhythm
The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase of...
Mechanism of Cardiac Arrhythmias
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
The Electrical Double Layer
In the region where two bulk phases meet, an intricate electric charge distribution arises due to charge transfer, ion adsorption, molecular orientation, and charge distortion. This complex distribution is commonly referred to as the electrical double layer.When a solid electrode interfaces with ions in an electrolyte solution, the speed of electron transfer dictates the rates of oxidation and reduction. The electrode acquires a charge through the escape of atoms into the solution as cations or...
