Toll-like receptor 3-stimulation and aggregate-formation synergistically enhances anti-inflammatory activity of feline mesenchymal stem cells.

IF 1.5 3区 农林科学 Q2 VETERINARY SCIENCES
Youhei Fujimoto, Shingo Hatoya, Kikuya Sugiura, Yasuhiko Tabata
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引用次数: 0

Abstract

Importance: Mesenchymal stem cells (MSCs) used to treat inflammatory diseases in humans show improved clinical outcomes compared to other treatments. On the other hand, feline MSCs have limited therapeutic effects because of their low bioactivity. Successful clinical treatment requires enhancing the anti-inflammatory ability of feline adipose-derived MSCs (fAdMSCs).

Objective: To enhance the anti-inflammatory activity of fAdMSCs.

Methods: fAdMSCs were treated with the toll-like receptor 3 (TLR3) ligand poly (I:C) and aggregated. Indoleamine 2,3-dioxygenase-1 (IDO-1) expression and kynurenine production were measured to evaluate the anti-inflammatory activity. Anti-inflammatory effects were assessed by culturing fAdMSCs with rat macrophages and transplanting them into the kidney capsules of rats.

Results: IDO-1 expression and kynurenine production in fAdMSCs were increased significantly by a poly (I:C) treatment and enhanced using a basic fibroblast growth factor (bFGF) treatment. The level of fAdMSC aggregation increased IDO-1 expression significantly compared to the monolayer. These effects were enhanced by pretreatment with bFGF and poly (I:C). The bFGF and poly (I:C)-pretreated fAdMSC aggregates suppressed tumor necrosis factor-α expression in rat macrophages. During transplantation, the pretreated fAdMSC aggregates avoided leakage, survived in aggregate form, and induced anti-inflammatory macrophages.

Conclusions and relevance: TLR3-stimulated, bFGF-pretreated fAdMSC aggregates increase the anti-inflammatory activity significantly, providing a potential therapeutic approach for inflammatory diseases in felines.

Toll 样受体 3 刺激和聚集体形成协同增强了猫间充质干细胞的抗炎活性。
重要性:与其他治疗方法相比,间充质干细胞(MSCs)用于治疗人类炎症性疾病显示出更好的临床结果。另一方面,由于猫间充质干细胞的生物活性较低,其治疗效果有限。成功的临床治疗需要增强猫脂肪源性间充质干细胞(fAdMSCs)的抗炎能力。目的:增强fAdMSCs的抗炎活性。方法:用toll样受体3 (TLR3)配体poly (I:C)处理fAdMSCs并聚集。检测吲哚胺2,3-双加氧酶-1 (IDO-1)表达和犬尿氨酸分泌,评价其抗炎活性。用大鼠巨噬细胞培养fAdMSCs,并将其移植到大鼠肾胶囊中,观察其抗炎作用。结果:IDO-1的表达和犬尿氨酸的产生在多聚(I:C)处理和碱性成纤维细胞生长因子(bFGF)处理下显著增加。与单层细胞相比,fAdMSC聚集水平显著增加IDO-1表达。经bFGF和聚(I:C)预处理后,这些效果得到增强。bFGF和poly (I:C)-预处理的fAdMSC聚集体可抑制大鼠巨噬细胞中肿瘤坏死因子-α的表达。在移植过程中,预处理的fAdMSC聚集体避免泄漏,以聚集体形式存活,并诱导抗炎巨噬细胞。结论及相关性:tlr3刺激、bfgf预处理的fAdMSC聚集体显著增加抗炎活性,为治疗猫炎症性疾病提供了一种潜在的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Veterinary Science
Journal of Veterinary Science 农林科学-兽医学
CiteScore
3.10
自引率
5.60%
发文量
86
审稿时长
1.3 months
期刊介绍: The Journal of Veterinary Science (J Vet Sci) is devoted to the advancement and dissemination of scientific knowledge concerning veterinary sciences and related academic disciplines. It is an international journal indexed in the Thomson Scientific Web of Science, SCI-EXPANDED, Sci Search, BIOSIS Previews, Biological Abstracts, Focus on: Veterinary Science & Medicine, Zoological Record, PubMed /MEDLINE, Index Medicus, Pubmed Central, CAB Abstracts / Index Veterinarius, EBSCO, AGRIS and AGRICOLA. This journal published in English by the Korean Society of Veterinary Science (KSVS) being distributed worldwide.
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