Microfibrous Scaffolds Guide Stem Cell Lumenogenesis and Brain Organoid Engineering.
Microfibrous Scaffolds Guide Stem Cell Lumenogenesis and Brain Organoid Engineering.
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微纤维支架引导干细胞腔发生和脑类器官工程。
DOI：
10.1002/adma.202300305
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Ritzau-Reid KI
中科院分区：
文献类型：
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作者：
Ritzau-Reid KI
三维类器官被广泛用作易于处理的体外模型，能够阐明人类发育和疾病的各个方面。然而，人工和低通量培养方法，加上低重复性和几何异质性，限制了类器官研究的范围和应用。结合干细胞生物学和生物工程的专业知识，为解决这些限制提供了一个有希望的方法。在这里，熔体静电纺丝书写被用来产生可调谐的网格支架，可以引导多能干细胞的自组织进入胚胎样体的图案阵列。网格几何被证明是干细胞自组织的关键决定因素，通过曲率控制的组织生长指导新兴管腔的位置和大小。报道了两种不同的方法将支架生长的胚状体培养成相互连接或空间离散的脑类器官。这些支架提供了一种高通量的方法来产生、培养和分析大量的类器官，大大减少了传统的类器官培养方法所涉及的时间投入和体力劳动。预计这一方法学的发展将为指导多能干细胞培养、研究放光发生以及产生大量用于高通量筛选的均匀类器官开辟新的机会。
3D organoids are 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, restrict 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, melt electrospinning writing is used to generate tuneable grid scaffolds that can guide the self‐organization of pluripotent stem cells into patterned arrays of embryoid bodies. Grid geometry is shown to be a key determinant of stem cell self‐organization, guiding the position and size of emerging lumens via curvature‐controlled tissue growth. Two distinct methods for culturing scaffold‐grown embryoid bodies into either interconnected or spatially discrete cerebral organoids are reported. These scaffolds provide a high‐throughput method to generate, culture, and analyze large numbers of organoids, substantially reducing the time investment and manual labor involved in conventional methods of organoid culture. It is anticipated 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.