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Cellular and Engineered Organoids for Cardiovascular Models
Circulation Research ( IF 20.1 ) Pub Date : 2022-06-09 , DOI: 10.1161/circresaha.122.320305
Dilip Thomas 1, 2 , Suji Choi 3 , Christina Alamana 1, 2 , Kevin Kit Parker 3, 4 , Joseph C Wu 1, 2, 5
Affiliation  

An ensemble of in vitro cardiac tissue models has been developed over the past several decades to aid our understanding of complex cardiovascular disorders using a reductionist approach. These approaches often rely on recapitulating single or multiple clinically relevant end points in a dish indicative of the cardiac pathophysiology. The possibility to generate disease-relevant and patient-specific human induced pluripotent stem cells has further leveraged the utility of the cardiac models as screening tools at a large scale. To elucidate biological mechanisms in the cardiac models, it is critical to integrate physiological cues in form of biochemical, biophysical, and electromechanical stimuli to achieve desired tissue-like maturity for a robust phenotyping. Here, we review the latest advances in the directed stem cell differentiation approaches to derive a wide gamut of cardiovascular cell types, to allow customization in cardiac model systems, and to study diseased states in multiple cell types. We also highlight the recent progress in the development of several cardiovascular models, such as cardiac organoids, microtissues, engineered heart tissues, and microphysiological systems. We further expand our discussion on defining the context of use for the selection of currently available cardiac tissue models. Last, we discuss the limitations and challenges with the current state-of-the-art cardiac models and highlight future directions.

中文翻译:

用于心血管模型的细胞和工程类器官

在过去的几十年里,已经开发了一套体外心脏组织模型,以帮助我们使用还原论方法理解复杂的心血管疾病。这些方法通常依赖于在指示心脏病生理学的培养皿中概括单个或多个临床相关终点。生成与疾病相关和患者特异性的人类诱导多能干细胞的可能性进一步利用了心脏模型作为大规模筛选工具的效用。为了阐明心脏模型中的生物学机制,以生物化学、生物物理学和机电刺激的形式整合生理线索以实现所需的组织样成熟度以实现稳健的表型分析是至关重要的。这里,我们回顾了定向干细胞分化方法的最新进展,以衍生出广泛的心血管细胞类型,允许在心脏模型系统中进行定制,并研究多种细胞类型的疾病状态。我们还重点介绍了几种心血管模型的最新进展,例如心脏类器官、微组织、工程心脏组织和微生理系统。我们进一步扩展了关于定义用于选择当前可用的心脏组织模型的使用环境的讨论。最后,我们讨论了当前最先进的心脏模型的局限性和挑战,并强调了未来的发展方向。我们还重点介绍了几种心血管模型的最新进展,例如心脏类器官、微组织、工程心脏组织和微生理系统。我们进一步扩展了关于定义用于选择当前可用的心脏组织模型的使用环境的讨论。最后,我们讨论了当前最先进的心脏模型的局限性和挑战,并强调了未来的发展方向。我们还重点介绍了几种心血管模型的最新进展,例如心脏类器官、微组织、工程心脏组织和微生理系统。我们进一步扩展了关于定义用于选择当前可用的心脏组织模型的使用环境的讨论。最后,我们讨论了当前最先进的心脏模型的局限性和挑战,并强调了未来的发展方向。
更新日期:2022-06-10
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