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工程化心脏组织与诱导多能干细胞:用于疾病建模、药物筛选及转化研究的宏观与微观结构

Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies.

作者信息

Tzatzalos Evangeline, Abilez Oscar J, Shukla Praveen, Wu Joseph C

机构信息

Stanford Cardiovascular Institute.

Institute for Stem Cell Biology and Regenerative Medicine.

出版信息

Adv Drug Deliv Rev. 2016 Jan 15;96:234-244. doi: 10.1016/j.addr.2015.09.010. Epub 2015 Sep 30.

Abstract

Engineered heart tissue has emerged as a personalized platform for drug screening. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. Subsequent developments in cardiovascular biology have led to efficient differentiation of cardiomyocytes, the force-producing cells of the heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless quantities of well-characterized, healthy, and disease-specific CMs, which in turn has enabled and driven the generation and scale-up of human physiological and disease-relevant engineered heart tissues. The combined technologies of engineered heart tissue and iPSC-CMs are being used to study diseases and to test drugs, and in the process, have advanced the field of cardiovascular tissue engineering into the field of precision medicine. In this review, we will discuss current developments in engineered heart tissue, including iPSC-CMs as a novel cell source. We examine new research directions that have improved the function of engineered heart tissue by using mechanical or electrical conditioning or the incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how engineered heart tissue can evolve into a powerful tool for therapeutic drug testing.

摘要

工程化心脏组织已成为药物筛选的个性化平台。随着诱导多能干细胞(iPSC)技术的出现,可以培养患者特异性干细胞并将其扩增为无限的细胞来源。心血管生物学的后续发展已实现心肌细胞(心脏中产生力量的细胞)的高效分化。源自iPSC的心肌细胞(iPSC-CM)提供了数量可能无限的、特征明确、健康且特定疾病的心肌细胞,这反过来又推动并促进了与人类生理和疾病相关的工程化心脏组织的生成和扩大规模。工程化心脏组织和iPSC-CM的联合技术正被用于研究疾病和测试药物,在此过程中,心血管组织工程领域已发展到精准医学领域。在本综述中,我们将讨论工程化心脏组织的当前发展情况,包括将iPSC-CM作为一种新型细胞来源。我们研究了通过机械或电调节或加入非心肌基质细胞来改善工程化心脏组织功能的新研究方向。最后,我们讨论工程化心脏组织如何能够发展成为治疗性药物测试的强大工具。

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