Department of Advanced Pathobiology, Graduate School of Veterinary Sciences, Osaka Metropolitan University, Osaka 598-0048, Japan.
Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
J Vet Sci. 2024 Nov;25(6):e86. doi: 10.4142/jvs.23330.
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).
To enhance the anti-inflammatory activity of fAdMSCs.
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.
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.
TLR3-stimulated, bFGF-pretreated fAdMSC aggregates increase the anti-inflammatory activity significantly, providing a potential therapeutic approach for inflammatory diseases in felines.
与其他治疗方法相比，用于治疗人类炎症性疾病的间充质干细胞（MSCs）显示出改善的临床结果。另一方面，由于猫间充质干细胞的生物活性低，其治疗效果有限。成功的临床治疗需要增强猫脂肪间充质干细胞（fAdMSCs）的抗炎能力。
增强 fAdMSCs 的抗炎活性。
用 Toll 样受体 3（TLR3）配体聚肌苷酸：聚胞苷酸（poly（I:C））和聚集物处理 fAdMSCs，以评估其抗炎活性。通过培养 fAdMSCs 与大鼠巨噬细胞并用其移植到大鼠肾囊中来评估抗炎效果。
poly（I:C）处理和碱性成纤维细胞生长因子（bFGF）处理可显著增加 fAdMSCs 中的吲哚胺 2,3-双加氧酶-1（IDO-1）表达和犬尿氨酸产生。与单层培养相比，fAdMSC 聚集物可显著增加 IDO-1 表达。这些作用通过 bFGF 和 poly（I:C）预处理增强。bFGF 和 poly（I:C）预处理的 fAdMSC 聚集物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 聚集物避免了渗漏，以聚集形式存活，并诱导抗炎巨噬细胞。
TLR3 刺激、bFGF 预处理的 fAdMSC 聚集物可显著增强抗炎活性，为猫的炎症性疾病提供了一种潜在的治疗方法。
