Human iPS cell based myocardial tissue as model of heart failure and cardiac assist device therapy: molecular characterization and identification of therapeutic strategies

基于人 iPS 细胞的心肌组织作为心力衰竭和心脏辅助装置治疗的模型：分子表征和治疗策略的识别

• 批准号: 317780100
• 负责人: Professorin Dr. Ina Gruh
• 金额: --
• 依托单位: Leibniz Forschungslaboratorien für Biotechnologie und künstliche Organe (LEBAO)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/317780100?language=en
• 关键词: Human; iPS; cell; based; myocardial

In TP5 we aim to establish an in vitro model of the failing myocardium and cardiac ventricular assist device therapy, in order to dissect molecular mechanisms of cardiac unloading in bioarticifial cardiac tissue (BCT) and to identify and test novel additive therapeutic approaches. For example, we will examine whether the anti-androgenic substance Finasteride, which according to our recent work exerts antihypertrophic and antifibrotic effects in the mouse myocardium, is able to improve the pathological changes of the failing BCT heart tissue when administered in addition to physical unloading. In a similar manner, we will analyze the impact of downregulating the prohypertrophic protein CIB1 or overexpression of the anti-hypertrophic protein TIP30. The BCTs will be generated from human iPS cells (from healthy donors as well as from patients with genetic cardiomyopathy) after their differentiation into cardiac myocytes. The BCTs will be subjected to controlled over-stretching, subsequent unloading and detailed functional, histological and molecular characterization.

在TP5中，我们的目标是建立衰竭心肌和心室辅助装置治疗的体外模型，以剖析生物人工心脏组织(BCT)心脏卸载的分子机制，并识别和测试新的附加治疗方法。例如，我们将研究抗雄激素物质非那雄胺，根据我们最近的工作，非那雄胺在小鼠心肌中发挥抗肥大和抗纤维化作用，在物理卸载的同时，是否能够改善正在衰竭的BCT心脏组织的病理变化。以类似的方式，我们将分析下调促肥厚性蛋白CIB1或过度表达抗肥厚性蛋白TIP30的影响。BCT将从人的iPS细胞(来自健康捐赠者和遗传性心肌病患者)分化为心肌细胞后产生。BCT将接受受控的过度拉伸、随后的卸载以及详细的功能、组织学和分子表征。