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Engineering    2017, Vol. 3 Issue (1) : 60-65     https://doi.org/10.1016/J.ENG.2017.01.011
Research |
人体胃肠道–菌群相互作用的工程学研究模型
Giolla Eain Marc Mac1,2,Baginska Joanna1,Greenhalgh Kacy1,Fritz Joëlle V.1,Zenhausern Frederic2,Wilmes Paul1()
1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, L 4362, Luxembourg
2. Center for Applied Nanobioscience and Medicine, University of Arizona, Tucson, AZ 85721, USA
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摘要 

研究宿主–胃肠道微生物的相互作用已经成为管理人类健康和疾病的关键组成部分。微生理系统的发展正在为研究人员提供前所未有的对于这种复杂关系的获取和理解。这些系统结合了微型工程、微流体和细胞培养的优点,来创建人类肠道中普遍存在的环境条件。在这里我们提出的HuMiX(人类微生物交联对话) 平台,是一个利用这种多学科方法提供具有代表性的人体胃肠道的体外模型系统,用于研究宿主–微生物分子的相互作用。我们总结了使用该平台获得的概念验证结果,强调其对于大大增强我们对宿主–微生物相互作用了解的潜力,且其可能对药物、食品和营养以及医疗保健行业产生的巨大影响。同时讨论了这些技术面临的一些关键问题和挑战。

关键词 微生物微流体肠道芯片HuMiX    
Abstract

Host-microbe interactions at the gastrointestinal interface have emerged as a key component in the governance of human health and disease. Advances in micro-physiological systems are providing researchers with unprecedented access and insights into this complex relationship. These systems combine the benefits of microengineering, microfluidics, and cell culture in a bid to recreate the environmental conditions prevalent in the human gut. Here we present the human-microbial cross talk (HuMiX) platform, one such system that leverages this multidisciplinary approach to provide a representative in vitro model of the human gastrointestinal interface. HuMiX presents a novel and robust means to study the molecular interactions at the host-microbe interface. We summarize our proof-of-concept results obtained using the platform and highlight its potential to greatly enhance our understanding of host-microbe interactions with a potential to greatly impact the pharmaceutical, food, nutrition, and healthcare industries in the future. A number of key questions and challenges facing these technologies are also discussed.

Keywords Microbiome      Microfluidics      Organ-on-a-chip      HuMiX     
基金资助: 
通讯作者: Wilmes Paul     E-mail: paul.wilmes@uni.lu
最新录用日期:    在线预览日期:    发布日期: 2017-03-02
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Marc Mac Giolla Eain
Joanna Baginska
Kacy Greenhalgh
Joë
lle V. Fritz
Frederic Zenhausern
Paul Wilmes
引用本文:   
Marc Mac Giolla Eain,Joanna Baginska,Kacy Greenhalgh, et al. Engineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface[J]. Engineering, 2017, 3(1): 60-65.
网址:  
http://engineering.org.cn/EN/10.1016/J.ENG.2017.01.011     OR     http://engineering.org.cn/EN/Y2017/V3/I1/60
Fig.1  The HuMiX platform [25]. (a) Image of the assembled HuMiX platform (the scale bar is equivalent to 1 cm); (b) exploded view of the HuMiX platform; (c) annotated schematic illustration of the key features in the HuMiX platform.
Fig.2  Data illustrating the ability of the HuMiX platform to sustain the co-culture of human and microbial cells [25]. (a) TEER measurements of the epithelial cell layer formed in HuMiX benchmarked against measurements from a standard Transwell system with error bars indicating the standard error of the mean (n= 3); (b) immunofluorescent microscopic image of the tight junction protein occluding (green) in Caco-2 cells following 24 h of co-culture with LGG grown under anaerobic conditions (the cell nuclei are stained with 4,6-diamidino-2-phenylindole and appear in blue); (c) fluorescent microscopic image of the live-dead stain of the Caco-2 cells 24 h post-culture; (d) fluorescent microscopic image of the live-dead stain of the LGG 24 h post-culture (the live cells appear in green whereas dead cells appear in red, and the scale bar is equivalent to 10 µm); (e) sample eluates from the three separate microchambers in HuMiX following 24 h of co-culture; (f) dissolved oxygen concentration levels (%) present within the perfusion and microbial chambers following inoculation of LGG (◆ denotes pre-inoculation levels in the microbial chamber).
Fig.3  Examples of genes, miRNAs, and metabolites found to be differentially abundant in Caco-2 cells following 24 h of co-culture with LGG growing under anaerobic conditions.
Fig.4  Schematic illustration of the nutri-HuMiX and the immuno-HuMiX platforms. Medium rich in fibers is perfused through the bacterial chamber in the nutri-HuMiX model. Primary immune cells are inoculated into the perfusion chamber in the immuno-HuMiX model.
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