IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Madeline K Eiken, Charlie J Childs, Lindy K Brastrom, Tristan Frum, Eleanor M Plaster, Donia W Ahmed, Ryan C Spencer, Orren Shachaf, Suzanne Pfeiffer, Justin E Levine, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Jason R Spence, Claudia Loebel
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引用次数: 0

摘要

人类诱导多能干细胞(iPSC)衍生的肺泡器官组织已成为模拟肺泡上皮细胞稳态和疾病的系统。然而,肺泡器官组织通常是在源自小鼠肉瘤的基底膜基质 Matrigel 中生长的,这种基质对基质特性的控制很差,这促使人们开发合成水凝胶作为 Matrigel 的替代品。在这里,我们开发了一种两步培养法,即先在基于水凝胶的微孔中预聚有机体,然后将其包埋在合成水凝胶中,这种方法支持肺泡有机体的生长,同时还能对有机体和水凝胶的特性进行很好的控制。我们发现,无论是在微孔中还是嵌入合成水凝胶后,聚集的类器官都会分泌其自身的新生细胞外基质(ECM),从而支持其生长。因此,本文所述的合成水凝胶使我们能够将外源 ECM 与新生 ECM 分离,从而研究 ECM 在类器官形成过程中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in synthetic hydrogels, which supports their growth. Thus, the synthetic hydrogels described here allow us to de-couple exogenous and nascent ECM to interrogate the role of ECM in organoid formation.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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