设计用于临床翻译的多细胞心脏组织工程技术

IF 6.2 2区 生物学 Q1 CELL BIOLOGY
Andrew R. Laskary , James E. Hudson , Enzo R. Porrello
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引用次数: 0

摘要

心血管疾病仍然是全世界死亡的主要原因——每年占所有死亡人数的三分之一。目前的二维体外细胞培养系统和动物模型不能完全概括这些疾病在人类中的临床复杂性。因此,迫切需要能够复制这些表型的高保真度生物系统,以告知临床结果和治疗发展。心脏组织工程(CTE)策略的出现是为了满足这一需求,通过设计体外三维心肌组织系统,从人类多能干细胞。通过这种方式,CTE系统可以作为高度可控的人体模型,用于各种应用,包括生理和病理建模、药物发现和临床前测试平台,甚至是临床中的直接治疗干预。尽管这些CTE技术的发展取得了重大进展,但仍然存在重大挑战,需要进行必要的改进,以获得更先进的人类心脏组织技术。在这篇综述中,我们提炼出该领域需要解决的三个重点领域:1)生成心肌细胞类型和可扩展的制造方法,2)工程组织结构,功能和分析,以及3)为特定应用策划系统设计。在我们的每个重点领域,我们强调设计能够模仿人类心脏复杂的细胞间连接的CTE系统的重要性,并讨论随后出现的基本设计考虑因素。最后,我们强调了使用CTE技术进行临床建模和直接修复受损和病变心脏的前沿应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Designing multicellular cardiac tissue engineering technologies for clinical translation
Cardiovascular diseases remain the leading cause of death worldwide—claiming one-third of all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate the clinical complexity of these diseases in humans. Therefore, there is a dire need for higher fidelity biological systems capable of replicating these phenotypes to inform clinical outcomes and therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged to fulfill this need by the design of in vitro three-dimensional myocardial tissue systems from human pluripotent stem cells. In this way, CTE systems serve as highly controllable human models for a variety of applications—including for physiological and pathological modeling, drug discovery and preclinical testing platforms, and even direct therapeutic interventions in the clinic. Although significant progress has been made in the development of these CTE technologies, critical challenges remain and necessary refinements are required to derive more advanced human heart tissue technologies. In this review, we distill three focus areas for the field to address: I) Generating cardiac muscle cell types and scalable manufacturing methods, II) Engineering tissue structure, function, and analyses, and III) Curating system design for specific application. In each of our focus areas, we emphasize the importance of designing CTE systems capable of mimicking the intricate intercellular connectivity of the human heart and discuss fundamental design considerations that subsequently arise. We conclude by highlighting cutting-edge applications that use CTE technologies for clinical modeling and the direct repair of damaged and diseased hearts.
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来源期刊
CiteScore
15.10
自引率
1.40%
发文量
310
审稿时长
9.1 weeks
期刊介绍: Seminars in Cell and Developmental Biology is a review journal dedicated to keeping scientists informed of developments in the field of molecular cell and developmental biology, on a topic by topic basis. Each issue is thematic in approach, devoted to an important topic of interest to cell and developmental biologists, focusing on the latest advances and their specific implications. The aim of each issue is to provide a coordinated, readable, and lively review of a selected area, published rapidly to ensure currency.
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