دورية أكاديمية
Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury
| العنوان: | Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury |
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| المؤلفون: | Jinjian Huang, Ziyan Xu, Jiao Jiao, Zongan Li, Sicheng Li, Ye Liu, Ze Li, Guiwen Qu, Jie Wu, Yun Zhao, Kang Chen, Jieshou Li, Yichang Pan, Xiuwen Wu, Jianan Ren |
| المصدر: | Bioactive Materials, Vol 30, Iss , Pp 1-14 (2023) |
| بيانات النشر: | KeAi Communications Co., Ltd., 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Materials of engineering and construction. Mechanics of materials LCC:Biology (General) |
| مصطلحات موضوعية: | Ionic barrier of ZIF-8, Microfluidics, Organoid-on-a-chip, Oxygen dynamics, Olfm4, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5 |
| الوصف: | Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2452-199X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2452199X23002062; https://doaj.org/toc/2452-199X |
| DOI: | 10.1016/j.bioactmat.2023.07.001 |
| URL الوصول: | https://doaj.org/article/61cc65f64c7445fcad04a02444ede9d6 |
| رقم الأكسشن: | edsdoj.61cc65f64c7445fcad04a02444ede9d6 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2452199X |
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| DOI: | 10.1016/j.bioactmat.2023.07.001 |