二维几何模板控制心脏类器官的形态和功能。

IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Plansky Hoang, Shiyang Sun, Bearett A Tarris, Zhen Ma
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引用次数: 0

摘要

传统上,组织特异性类器官是由嵌入在基质或水凝胶中的干细胞的3D聚集体产生的,聚集体最终形成球形并悬浮在基质中。由于缺乏对类器官形成的几何控制,使得这些球形类器官在复杂形状组织的建模中受到限制。为了解决这一挑战,我们开发了一种新的方法,从2D微模式人类诱导多能干细胞(hiPSC)菌落中生成3D空间组织的心脏类器官,而不是直接从3D干细胞聚集体中生成。这种新方法为创建2D非球形几何模板的心脏类器官提供了可能性,这可能使我们对发育器官发生的生物物理控制有了更深入的了解。本文设计了总面积相同但几何形状不同的四边形和五角形二维几何模板。利用该模板底物,我们从hipsc中培养心脏类器官,并收集了一系列参数来表征心脏类器官的形态和功能特性。在四边形模板中,我们发现增加长宽比会损害心脏组织的3D自组装,但延长的几何形状会改善心脏的收缩功能。然而,在五角星模板中,心脏类器官的结构和功能被优化为理想的星形的特定几何形状。这项研究将通过增加从外部几何线索开始模板的复杂性来改善类器官的形态发生和功能,从而阐明“通过设计的器官发生”。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Controlling Morphology and Functions of Cardiac Organoids by Two-Dimensional Geometrical Templates.

Traditionally, tissue-specific organoids are generated as 3D aggregates of stem cells embedded in Matrigel or hydrogels, and the aggregates eventually end up a spherical shape and suspended in the matrix. Lack of geometrical control of organoid formation makes these spherical organoids limited for modeling the tissues with complex shapes. To address this challenge, we developed a new method to generate 3D spatial-organized cardiac organoids from 2D micropatterned human induced pluripotent stem cell (hiPSC) colonies, instead of directly from 3D stem cell aggregates. This new approach opens the possibility to create cardiac organoids that are templated by 2D non-spherical geometries, which potentially provides us a deeper understanding of biophysical controls on developmental organogenesis. Here, we designed 2D geometrical templates with quadrilateral shapes and pentagram shapes that had same total area but different geometrical shapes. Using this templated substrate, we grew cardiac organoids from hiPSCs and collected a series of parameters to characterize morphological and functional properties of the cardiac organoids. In quadrilateral templates, we found that increasing the aspect ratio impaired cardiac tissue 3D self-assembly, but the elongated geometry improved the cardiac contractile functions. However, in pentagram templates, cardiac organoid structure and function were optimized with a specific geometry of an ideal star shape. This study will shed a light on "organogenesis-by-design" by increasing the intricacy of starting templates from external geometrical cues to improve the organoid morphogenesis and functionality.

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来源期刊
Cells Tissues Organs
Cells Tissues Organs 生物-发育生物学
CiteScore
4.90
自引率
3.70%
发文量
45
审稿时长
6-12 weeks
期刊介绍: ''Cells Tissues Organs'' aims at bridging the gap between cell biology and developmental biology and the emerging fields of regenerative medicine (stem cell biology, tissue engineering, artificial organs, in vitro systems and transplantation biology). CTO offers a rapid and fair peer-review and exquisite reproduction quality. Special topic issues, entire issues of the journal devoted to a single research topic within the range of interests of the journal, are published at irregular intervals.
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