应用方向肠道类器官应用于治疗DSS诱导的溃疡性结肠炎

溃疡性结肠炎(ulcerative colitis，UC)是一种慢性非特异性结肠炎性反应，病变主要位于结肠的黏膜层，临床表现为持续或反复发作的腹泻、黏液脓血样便伴腹痛，该病病程长，治愈难度大，且与结肠癌关系密切，属于消化系统难治疾病之一。

随着近些年细胞治疗的发展，研究人员也开始在细胞领域探索新的治疗方法。随着类器官研究的大热，肠道干细胞成为肠道损伤再生、肠癌等多种肠道疾病研究的焦点。

随着近些年细胞治疗的发展，类器官这个词，也从陌生逐渐被熟知。

肠道类器官的培养——将分离的肠道隐窝或干细胞植入含有多种生长因子的基质胶中，在基质3D支撑下生成具有肠道上皮样结构的微型空心球体，这些球体被称为肠道类器官。这些类器官包含有所有种类的肠道功能上皮细胞，可以较大程度模拟肠道组织，可被广泛应用于炎症性肠病、肠道损伤再生、肠癌等多种肠道疾病的研究。

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图1小鼠小肠类器官体外培养结果图

日本东京医科齿科大学（TMDU）研究团队提出了一个详细方案，用移植的3D干细胞类器官结构来再生在结肠中受损的肠道组织。

利用干细胞的再生能力，使用肠道类器官来替代受损的肠道组织。通常情况下，溃疡性结肠炎的大部分上皮细胞受损，为了开发将肠类器官移植到结肠的系统，研究人员使用硫酸葡聚糖钠（DSS）损伤模型，通过一根柔性导管将类器官注入患有结肠炎的小鼠结肠中，并用胶水封闭肛门边缘，使培养的上皮细胞能够完全附着在受损表明并填充干细胞壁龛。实验结果表明，肠道内壁其中受体的部分几乎完整的上皮衬里已被供体细胞所取代。

目前有多种动物模型被广泛用于研究炎症性肠炎（inflammatory bowel disease，IBD）的病因、发病机制及测试新开发药物药效等，尤其以葡聚糖硫酸钠盐结肠炎（ulcerative colitis，UC）模型应用最广。

YEASEN提供高品质葡聚糖硫酸钠盐（Dextran Sulfate Sodium Salt，DSS MW:36000~50000），Cat#60316ES，高纯度（98%），含硫量（16-20%），游离硫（<0.2%）。

1. 小鼠体重下降

图2Yeasen DSS（货号：60316ES，批号：D1124051）造模数据（C57/B6J，雌鼠，8 周龄）

2. 小鼠结肠炎H&E染色结果

图3 H&E染色结果（Gao X, et al. The Journal of Nutritional Biochemistry, 2020, 83.）

l 实验动物: BALB/c，雌性，6-8 周龄，25 g

l 实验方法: 3.5% DSS自由饮水7天

3. 小鼠结肠癌H&E染色结果

图4 H&E染色结果（Jia-Rong Huang, et al.Frontiers in Pharmacology.2020.586885）

l 实验动物: BALB/c，雄性，7周龄

l DSS浓度: 2.5%

l AOM浓度:10 mg/kg

l 实验周期:10周

结肠炎建模

[1] Li Zhao, Fei Wang,Zhengwei Cai,et al.Improving drug utilization platform with injectable mucoadhesive hydrogel for treating ulcerative colitis[J].chemical engineering journal.424(2021)130464.IF=16.744

[2] Lingjun Tong, Haining Hao, Zhe Zhang,et al.Milk-derived extracellular vesicles alleviate ulcerative colitis by regulating the gut immunity and reshaping the gut microbiota[J].Theranostics.2021; 11(17): 8570-8586 IF=11.556

[3] Li, Y., Dong, J., Xiao, H., Zhang, S., Wang, B., Cui, M., & Fan, S. Gut commensal derived-valeric acid protects against radiation injuries. Gut Microbes,.2020 .1–18.IF=10.245

[4] Jingjing Gan, Yuxiao Liu, Lingyu Sun,et al.Orally administrated nucleotide-delivery particles from microfluidics for inflammatory bowel disease treatment[J].Applied Materials Today.2021 Dec;25:101231 IF=10.041

[5] Mengmeng Xu, Ying Kong, Nannan Chen,et al.Identification of Immune-Related Gene Signature and Prediction of CeRNA Network in Active Ulcerative Colitis[J].Frontiers in Immunology.2022; 13: 855645. IF=7.561

[6] JialiDong,YuanLi,HuiwenXiao,et al.Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models[J].Cell reports.2021, 109886.IF=9.423

[7] Hao H, Zhang X, Tong L, Liu Q,et al.Lactobacillus plantarumEffect of Extracellular Vesicles Derived From Q7 on Gut Microbiota and Ulcerative Colitis in Mice[J].Frontiers in Immunology.2021.777147 .IF=7.561

[8] Yaohua Fan,Yanqun Fan,Kunfeng Liu,et al.Edible Bird’s Nest Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57BL/6J Mice by Restoring the Th17/Treg Cell Balance[J].Frontiers in Pharmacology.2021.632602.IF=7.561

[9] Jia-Rong Huang, Sheng-Te Wang, Meng-Ning Wei,et al.Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer[J].Frontiers in Pharmacology.2020.586885. IF=7.561

[10] Gao X, Fan W, Tan L, et al. Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways[J]. The Journal of Nutritional Biochemistry, 2020, 83.IF=6.048

[11] Lujuan Xing, Lijuan Fu, Songmin Cao,et al.The Anti-Inflammatory Effect of Bovine Bone-Gelatin-Derived Peptides in LPS-Induced RAW264.7 Macrophages Cells and Dextran Sulfate Sodium-Induced C57BL/6 Mice[J]. Nutrients 2022, 14, 1479. IF=5.717

[12] Wang S, Huang J, Tan KS, et al.Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-B Pathway[J].Oxidative Medicine and Cellular Longevity. 2022,4636618. IF=5.076