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人脐带间充质干细胞改善Ⅱ型胶原诱导的关节炎大鼠的免疫相关炎症和血栓前状态。

Human umbilical cord mesenchymal stem cells improve the immune-associated inflammatory and prothrombotic state in collagen type-Ⅱ-induced arthritic rats.

作者信息

Gu Jian, Gu Wei, Lin Chuanming, Gu Hao, Wu Wei, Yin Jie, Ni Jun, Pei Xiaoping, Sun Mei, Wang Fangfang, Li Zou, Cai Xinzheng, Ren Minmin, Yu Zhang, Gu Xiang

机构信息

Department of Hematology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, P.R. China.

Jiangsu Province Brain Hospital, Nanjing, Jiangsu 210000, P.R. China.

出版信息

Mol Med Rep. 2015 Nov;12(5):7463-70. doi: 10.3892/mmr.2015.4394. Epub 2015 Sep 30.

Abstract

Human umbilical cord mesenchymal stem cells (hUC‑MSCs) hold great potential in the search for therapies to treat refractory diseases, including rheumatoid arthritis (RA), due to their potential regenerative ability and extensive source. However, the role of hUC‑MSCs in vivo and the repair mechanisms for RA remain to be fully elucidated. The present study aimed to determine whether hUC‑MSCs exert immunomodulatory effects and have anti‑inflammatory capabilities in the treatment of embolisms. Following the transplantation of hUC‑MSCs into collagen type Ⅱ‑induced arthritic (CIA) model rats, magnetic resonance imaging (MRI) in vivo was performed, and the levels of interleukin (IL)‑1, IL‑17, tumor necrosis factor (TNF)‑α, vascular endothelial growth factor (VEGF), tissue factor (TF), CD4+CD25+ T cells (Treg) and antithrombin (AT) were measured. Bromodeoxyuridine staining was performed for histopathological examinations. As revealed by immunofluorescence and MRI experiments, the injected hUC‑MSCs preferentially migrated to the inflammatory joint sites of the rats. The Treg cell percentage and AT levels in the hUC‑MSC‑treated group were markedly increased, whereas the levels of IL‑1, IL‑17, TNF‑α, VEGF and TF were decreased compared with those in the CIA model group. The values determined for these parameters in the hUC‑MSC‑treated group returned to approximately the identical values as those of the control group on day 35 post‑therapy. Superparamagnetic iron oxide nanoparticles (SPIONs) may serve as an effective, non‑invasive method for tracking transplanted cells in vivo. The present study provided direct evidence that hUC‑MSCs in the CIA rat model migrated to the inflammatory joint sites, effectively promoting recovery from collagen type II damage and thereby improving the immune‑associated prothrombotic state.

摘要

人脐带间充质干细胞(hUC-MSCs)因其潜在的再生能力和丰富的来源,在寻找治疗难治性疾病(包括类风湿性关节炎(RA))的疗法方面具有巨大潜力。然而,hUC-MSCs在体内的作用以及RA的修复机制仍有待充分阐明。本研究旨在确定hUC-MSCs在治疗栓塞中是否发挥免疫调节作用并具有抗炎能力。将hUC-MSCs移植到Ⅱ型胶原诱导的关节炎(CIA)模型大鼠后,进行体内磁共振成像(MRI),并测量白细胞介素(IL)-1、IL-17、肿瘤坏死因子(TNF)-α、血管内皮生长因子(VEGF)、组织因子(TF)、CD4+CD25+T细胞(Treg)和抗凝血酶(AT)的水平。进行溴脱氧尿苷染色以进行组织病理学检查。免疫荧光和MRI实验表明,注射的hUC-MSCs优先迁移到大鼠的炎症关节部位。与CIA模型组相比,hUC-MSCs治疗组的Treg细胞百分比和AT水平显著升高,而IL-1、IL-17、TNF-α、VEGF和TF水平降低。在治疗后第35天,hUC-MSCs治疗组中这些参数的测定值恢复到与对照组大致相同的值。超顺磁性氧化铁纳米颗粒(SPIONs)可作为一种有效、非侵入性的方法用于体内追踪移植细胞。本研究提供了直接证据,表明CIA大鼠模型中的hUC-MSCs迁移到炎症关节部位,有效促进从Ⅱ型胶原损伤中恢复,从而改善免疫相关的血栓前状态。

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