地塞米松治疗保留了成人心脏外植体的结构并支持其在体外的长期收缩性

L. Eisenberg, Keerat Kaur, John M. Castillo, John G. Edwards, C. Eisenberg
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引用次数: 0

摘要

正常的心肌收缩功能对最佳的心血管健康至关重要。在细胞水平上评价药物对心肌细胞功能的影响是长期研究的难点。目前的培养系统依赖于分离的心肌细胞制剂或多能干细胞(PSCs)衍生的心肌细胞,所有这些都有局限性。分离的内源性心肌细胞在培养中长期不能保持收缩。虽然psc衍生的心肌细胞表现出较长时间的收缩活性,但它们的表型比成人更像胚胎。在这里,我们报告了地塞米松(DEX)治疗成年小鼠心房组织可以延长其在培养中的功能。正常情况下,心脏外植体在第一个月内就会失去收缩组织的能力,因为组织变平并在培养基质上扩散,同时细胞去分化并失去心肌表型。然而,在DEX治疗下,心脏外植体可维持其收缩功能、3D形态和心肌细胞表型长达6个月。此外,DEX还保留了离体大鼠心肌细胞的收缩表型。DEX的这些数据表明,对培养条件进行简单的修改可以大大提高体外模型系统筛选可用于缓解人类心脏病的药物和制剂的长期效用。
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Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro
Normal contractile function of the myocardium is essential for optimal cardiovascular health. Evaluating drug effects on cardiomyocyte function at the cellular level is difficult for long-term studies. Present culture systems rely on isolated, cardiomyocyte preparations or cardiomyocytes derived from pluripotent stem cells (PSCs), all of which have limitations. Isolated, endogenous cardiomyocytes do not remain contractile in culture long term. While PSC-derived cardiomyocytes show contractile activity for longer periods of time, their phenotype is more embryonic than adult. Here we report that dexamethasone (DEX) treatment of adult mouse atrial tissue can extend its functionality in culture. Normally, cardiac explants cease their capacity as a contractile tissue within the first month, as the tissue flattens and spreads out on the culture substrate, while the cells dedifferentiate and lose their myocardial phenotype. However, with DEX treatment, cardiac explants maintain their contractile function, 3D morphology, and myocyte phenotype for up to 6 months. Moreover, DEX also preserved the contractile phenotype of isolated rat cardiomyocytes. These data with DEX suggest that simple modifications in culture conditions can greatly improve the long-term utility of in vitro model systems for screening drugs and agents that could be employed to alleviate human cardiac disease.
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来源期刊
Journal of International Translational Medicine
Journal of International Translational Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
自引率
0.00%
发文量
317
审稿时长
8 weeks
期刊介绍: Journal of International Translational Medicine (JITM, ISSN 2227-6394), founded in 2012, is an English academic journal published by Journal of International Translational Medicine Co., Ltd and sponsored by International Fderation of Translational Medicine. JITM is an open access journal freely serving to submit, review, publish, read and download full text and quote. JITM is a quarterly publication with the first issue published in March, 2013, and all articles published in English are compiled and edited by professional graphic designers according to the international compiling and editing standard. All members of the JITM Editorial Board are the famous international specialists in the field of translational medicine who come from twenty different countries and areas such as USA, Britain, France, Germany and so on.
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