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定制水凝胶作为小鼠急性结肠炎模型中间充质干细胞条件培养基的递送平台

Tailored Hydrogels as Delivery Platforms for Conditioned Medium from Mesenchymal Stem Cells in a Model of Acute Colitis in Mice.

作者信息

Sendon-Lago Juan, Rio Lorena Garcia-Del, Eiro Noemi, Diaz-Rodriguez Patricia, Avila Leandro, Gonzalez Luis O, Vizoso Francisco J, Perez-Fernandez Roman, Landin Mariana

机构信息

Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Department of Physiology, Universidade de Santiago de Compostela, Avda. de Barcelona 22, 15706 Santiago de Compostela, Spain.

Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

出版信息

Pharmaceutics. 2021 Jul 23;13(8):1127. doi: 10.3390/pharmaceutics13081127.

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.

摘要

炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),正日益普遍,而目前的治疗方法并不完全有效。间充质干细胞正成为一种有前景的治疗选择。在此,已评估了在实验性急性结肠炎小鼠模型中局部应用负载人子宫颈干细胞条件培养基(hUCESC-CM)的水凝胶的效果。通过将葡聚糖硫酸钠(DSS)溶解于饮用水中9天,在C57BL/6小鼠中诱导结肠炎。通过直肠给药美沙拉嗪(作为阳性对照)或负载hUCESC-CM的粘膜粘附性热敏水凝胶(H-hUCESC-CM)来治疗溃疡。评估体重变化、结肠长度和组织病理学分析。此外,通过qPCR测量促炎细胞因子TNF-α、IL-6和IFN-γ的mRNA水平。用H-hUCESC-CM治疗可抑制体重减轻和结肠缩短,并导致结肠粘膜变性以及TNF-α、IFN-γ和IL-6 mRNA水平显著降低。结果表明,H-hUCESC-CM可有效减轻小鼠DSS诱导的结肠炎,提示H-hUCESC-CM可能是一种有吸引力的用于IBD局部治疗的无细胞疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bec/8400526/84b555168258/pharmaceutics-13-01127-g001.jpg

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