APPLICATION OF MULTIPOTENT MESENCHYMAL STEM CELL SECRETOME IN THE TREATMENT OF ADJUVANT ARTHRITIS AND CONTACT-ALLERGIC DERMATITIS IN ANIMAL MODELS

P. A. Golubinskaya, M. V. Sarycheva, A. Dolzhikov, V. Bondarev, M. Stefanova, V. Soldatov, S. Nadezhdin, M. V. Korokin, M. Pokrovsky, Yuriy E. Burda
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引用次数: 1

Abstract

The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods. Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results. Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2nd day. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3rd day of application, the negative control - on the 4th day. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion. The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.
多能间充质干细胞分泌组在佐剂性关节炎和接触性过敏性皮炎动物模型中的应用
多能间充质干细胞的治疗作用已在多种疾病模型中得到证实。其中一种机制是细胞对周围组织的旁分泌作用。的目标。探讨多能间充质干细胞治疗Wistar大鼠佐剂性关节炎和接触性过敏性皮炎的分泌组效应。材料和方法。用弗氏完全佐剂模拟26只雌性大鼠的佐剂性关节炎,然后用100µl多能间充质干细胞分泌组或生理盐水治疗。将200 μl二硝基氟苯油溶液分别于第1、5、6天滴入30只雌性大鼠皮肤,建立接触性过敏性皮炎模型。然后用氟西诺酮软膏(阳性对照)、婴儿乳膏(阴性对照)、含有天然多能间充质干细胞分泌组的婴儿乳膏或由地塞米松处理的细胞分泌组治疗大鼠。从大鼠爪纵、横尺寸指标及组织学检查来看,分泌组对佐剂性关节炎无抗炎作用。地塞米松处理的多能间充质干细胞的秘密乳膏对接触性过敏性皮炎模型最有效:临床改善发生在第2天。天然多能间充质干细胞分泌组和氟西诺酮在应用第3天出现治疗效果,第4天为阴性对照。所有病例淋巴细胞浸润系数均显著低于阴性对照组(2.8±0.1)(p <0.05)。而使用天然间充质干细胞分泌组(1.75±0.1)和地塞米松刺激的多能间充质干细胞分泌组(1.76±0.1)时,浸润率最低。在接触性过敏性皮炎模型上,含有多能间充质干细胞分泌组的乳膏比外用高活性糖皮质激素氟西诺酮对淋巴细胞浸润的抑制作用更强,这是一种典型的局部迟发性超敏反应。然而,在从大分子蛋白中初步纯化后,需要进一步研究分泌组对全身性炎症疾病模型的治疗作用。
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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