3D bioengineered tissue model of the large intestine to study inflammatory bowel disease
3D bioengineered tissue model of the large intestine to study inflammatory bowel disease
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DOI：
10.1016/j.biomaterials.2019.119517
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发表时间：
2019-12-01
期刊：
影响因子：
14
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Roh, Terrence T.;Chen, Ying;Kaplan, David L.
具有免疫组分的肠上皮的体外模型被生物工程化以模拟在炎症性肠病中观察到的免疫应答。虽然可以在transwell和2D培养系统中对肠道免疫现象进行建模，但3D组织模型通过提供3D基质来改善生理相关性，所述3D基质能够使巨噬细胞向上皮迁移。使用海绵状生物材料支架对由非转化的人结肠类器官细胞组成的肠上皮层和充满单核细胞衍生的巨噬细胞的上皮下层进行生物工程改造以模拟天然肠粘膜细胞组织。观察到具有微绒毛的融合单层、粘液层和巨噬细胞浸润至上皮基底侧。E. coli O 111：B4脂多糖和干扰素γ导致上皮细胞的形态学变化，导致球状结构，上皮覆盖减少，巨噬细胞向上皮细胞的迁移增加。对炎症组织模型中存在的细胞因子的分析表明，促炎细胞因子的分泌显著上调，这些促炎细胞因子通常与活动性炎症性肠病相关，包括CXCL 10、IL-β、IL-6、MCP-2和MIP-1 β。巨噬细胞层增强了上皮细胞和生化反应的炎症损伤，这种新的组织系统可能是有用的研究和开发潜在的治疗炎症性肠病。
An in vitro model of intestinal epithelium with an immune component was bioengineered to mimic immunologic responses seen in inflammatory bowel disease. While intestinal immune phenomena can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelial layer comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy biomaterial scaffolds. Confluent monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon gamma resulted in morphological changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and increased migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines that are often associated with active inflammatory bowel disease, including CXCL10, IL-beta, IL-6, MCP-2, and MIP-1 beta. The macrophage layer enhanced epithelial and biochemical responses to inflammatory insult, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease.