小柯机器人

美国宾夕法尼亚大学Dan Dongeun Huh研究小组报道在培养皿中增加器官发生的类器官培养几何工程。这一研究成果于2022年10月24日发表在国际学术期刊《自然-方法学》上。

在本研究中，研究人员介绍一种简单、可扩展的工程方法，以实现类器官的长期发育和成熟。研究人员改变了传统类器官培养物的组成，以开发一个平台将干细胞悬浮液的单次注射转化为放射状类器官阵列，这些细胞的细胞周期可以长时间维持而无需传代。使用该系统，研究人员展示了肠道类器官的加速生产，其结构和功能成熟度显著增加，并且持续发育超过了4周。

此外，研究人员还构建了一种患者来源的炎症性肠病（IBD）类器官模型，并使用单细胞RNA测序对其进行了检测，以证明其可再现IBD的标志病理特征。最后，研究人员对该方法进行了扩展，以设计血管化的可灌注人肠类化合物，可用于模拟IBD的先天免疫反应。这项工作提供了一种简易的平台技术，用于在培养皿中实现类器官状结构的生成。

附：英文原文

Title: Geometric engineering of organoid culture for enhanced organogenesis in a dish

Author: Park, Sunghee Estelle, Kang, Shawn, Paek, Jungwook, Georgescu, Andrei, Chang, Jeehan, Yi, Alex Yoon, Wilkins, Benjamin J., Karakasheva, Tatiana A., Hamilton, Kathryn E., Huh, Dan Dongeun

Issue&Volume: 2022-10-24

Abstract: Here, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.

DOI: 10.1038/s41592-022-01643-8

Source: https://www.nature.com/articles/s41592-022-01643-8

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex