Human Tissue-Engineered Model of Myocardial Ischemia-Reperfusion Injury
Human Tissue-Engineered Model of Myocardial Ischemia-Reperfusion Injury
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DOI：
10.1089/ten.tea.2018.0212
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发表时间：
2018-11-20
影响因子：
4.1
通讯作者：
Vunjak-Novakovic, Gordana
中科院分区：
文献类型：
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作者：
Chen, Timothy;Vunjak-Novakovic, Gordana
缺血再灌注损伤（IRI）是急性心肌梗死后最终组织损伤的主要因素，但有可能是可预防的。许多治疗方法在临床前环境中成功地减少了IRI，但在临床研究中没有一种显示出改善的结果。将新疗法转化为临床环境的部分失败可归因于临床前研究中对小动物模型的依赖。虽然动物模型概括了体内系统环境的复杂性，但它们并不一定概括了人类生理学。在本研究中，我们利用心脏组织工程方法和人类诱导多能干细胞衍生的心肌细胞建立了人类IRI组织工程模型。由此产生的心脏结构受到模拟缺血再灌注的条件。我们证明了再灌注损伤的存在以及区分缺血和再灌注损伤的能力。我们还证明了缺血预处理、再灌注条件的改善和增加心脏保护治疗后IRI的减少。本研究建立了人体组织模型的效用，用于研究IRI的关键方面，并有可能改善将治疗策略转化为临床环境。
Ischemia-reperfusion injury (IRI) is a major, but potentially preventable contributor to the final tissue damage after an acute myocardial infarction. Many therapies have demonstrated successful reduction of IRI in preclinical settings, but none has shown improved outcomes in clinical studies. Part of the failure to translate new therapies to clinical settings can be attributed to the reliance on small animal models in preclinical studies. While animal models encapsulate the complexity of the systemic in vivo environment, they do not necessarily recapitulate human physiology. In this study, we utilized cardiac tissue engineering methods and cardiomyocytes derived from human induced pluripotent stem cells to establish a human tissue-engineered model of IRI. The resulting cardiac constructs were subjected to conditions that simulated ischemia-reperfusion. We demonstrated the presence of reperfusion injury and the ability to distinguish ischemic and reperfusion injury. We also demonstrated reductions in IRI following ischemic preconditioning, modification of reperfusion conditions, and addition of cardioprotective therapeutics. This study establishes the utility of a human tissue model for studying key aspects of IRI and the potential for improving translation of therapeutic strategies into the clinical setting.