微纤维支架引导干细胞管腔生成及脑器官工程化的研究。
Microfibrous Scaffolds Guide Stem Cell Lumenogenesis and Brain Organoid Engineering.
发表日期:2023 Aug 12
作者:
Kaja I Ritzau-Reid, Sebastien J P Callens, Ruoxiao Xie, Martina Cihova, Daniel Reumann, Christopher L Grigsby, Lino Prados-Martin, Richard Wang, Axel C Moore, James P K Armstrong, Juergen A Knoblich, Molly M Stevens
来源:
Stem Cell Research & Therapy
摘要:
三维器官结构已广泛应用作为可追踪的体外模型,用于阐明人类发育和疾病的方面。然而,人工和低通量的培养方法,以及低可重复性和几何异质性限制了器官结构研究的范围和应用。结合干细胞生物学和生物工程领域的专业知识,为解决这些限制提供了一种有希望的方法。在这里,我们使用熔融静电纺丝写入技术生成可调控的网格支架,可以引导多能干细胞自组织成图案排列的胚胎体。我们展示了网格几何结构是干细胞自组织的关键因素,通过曲率控制的组织生长,引导出发生的腔隙的位置和大小。我们报道了两种不同的方法,将获得胚胎体的网格培养到连通或空间离散型的脑器官结构。这些支架提供了一种高通量方法,用于生成、培养和分析大量器官结构,大大降低了传统器官结构培养方法所需的时间投资和人工劳动。我们预计,这种方法的发展将在引导多能干细胞培养、研究腔隙形成以及生成大量均匀器官结构进行高通量筛选方面开辟新的机会。本文受版权保护。版权所有。
3D organoids have been widely used as tractable in vitro models capable of elucidating aspects of human development and disease. However, the manual and low throughput culture methods coupled with a low reproducibility and geometric heterogeneity restricts the scope and application of organoid research. Combining expertise from stem cell biology and bioengineering offers a promising approach to address some of these limitations. Here, we use melt electrospinning writing to generate tuneable grid scaffolds that can guide the self-organization of pluripotent stem cells into patterned arrays of embryoid bodies. We show that grid geometry is a key determinant of stem cell self-organization, guiding the position and size of emerging lumens via curvature-controlled tissue growth. We report two distinct methods for culturing scaffold-grown embryoid bodies into either interconnected or spatially discrete cerebral organoids. These scaffolds provide a high-throughput method to generate, culture and analyse large numbers of organoids, substantially reducing the time investment and manual labour involved in conventional methods of organoid culture. We anticipate that this methodological development will open up new opportunities for guiding pluripotent stem cell culture, studying lumenogenesis, and generating large numbers of uniform organoids for high throughput screening. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.