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用于研究与中性粒细胞相互作用的三重共培养和灌注生物反应器:一种用于细菌感染和免疫的新型三维组织模型。

Triple co-culture and perfusion bioreactor for studying the interaction between and neutrophils: A novel 3D tissue model for bacterial infection and immunity.

作者信息

Heydarian Motaharehsadat, Schweinlin Matthias, Schwarz Thomas, Rawal Ravisha, Walles Heike, Metzger Marco, Rudel Thomas, Kozjak-Pavlovic Vera

机构信息

Biocenter, Chair of Microbiology, University of Würzburg, Würzburg, Germany.

Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.

出版信息

J Tissue Eng. 2021 Jan 28;12:2041731420988802. doi: 10.1177/2041731420988802. eCollection 2021 Jan-Dec.

DOI:10.1177/2041731420988802
PMID:33796248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7970704/
Abstract

Gonorrhea, a sexually transmitted disease caused by the bacteria , is characterized by a large number of neutrophils recruited to the site of infection. Therefore, proper modeling of the interaction with neutrophils is very important for investigating and understanding the mechanisms that gonococci use to evade the immune response. We have used a combination of a unique human 3D tissue model together with a dynamic culture system to study neutrophil transmigration to the site of infection. The triple co-culture model consisted of epithelial cells (T84 human colorectal carcinoma cells), human primary dermal fibroblasts, and human umbilical vein endothelial cells on a biological scaffold (SIS). After the infection of the tissue model with , we introduced primary human neutrophils to the endothelial side of the model using a perfusion-based bioreactor system. By this approach, we were able to demonstrate the activation and transmigration of neutrophils across the 3D tissue model and their recruitment to the site of infection. In summary, the triple co-culture model supplemented by neutrophils represents a promising tool for investigating and other bacterial infections and interactions with the innate immunity cells under conditions closely resembling the native tissue environment.

摘要

淋病是一种由细菌引起的性传播疾病,其特征是大量中性粒细胞被招募到感染部位。因此,正确模拟与中性粒细胞的相互作用对于研究和理解淋球菌用于逃避免疫反应的机制非常重要。我们使用了独特的人类3D组织模型与动态培养系统相结合的方法来研究中性粒细胞向感染部位的迁移。三重共培养模型由上皮细胞(T84人结肠癌细胞)、人原代表皮成纤维细胞和人脐静脉内皮细胞在生物支架(小肠黏膜下层)上组成。在用淋病奈瑟菌感染组织模型后,我们使用基于灌注的生物反应器系统将原代人中性粒细胞引入模型的内皮侧。通过这种方法,我们能够证明中性粒细胞在3D组织模型中的激活和迁移以及它们被招募到感染部位。总之,补充了中性粒细胞的三重共培养模型是一种很有前途的工具,可用于在与天然组织环境非常相似的条件下研究淋病及其他细菌感染以及与先天免疫细胞的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/b69747d22cb4/10.1177_2041731420988802-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/45e1f60447b1/10.1177_2041731420988802-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/917b5924d595/10.1177_2041731420988802-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/4821472fed88/10.1177_2041731420988802-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/8fa9c6f2a07e/10.1177_2041731420988802-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/96e4ce9c8df6/10.1177_2041731420988802-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/b69747d22cb4/10.1177_2041731420988802-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/45e1f60447b1/10.1177_2041731420988802-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/917b5924d595/10.1177_2041731420988802-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/4821472fed88/10.1177_2041731420988802-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/8fa9c6f2a07e/10.1177_2041731420988802-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/96e4ce9c8df6/10.1177_2041731420988802-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a1d/7970704/b69747d22cb4/10.1177_2041731420988802-fig6.jpg

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