小鼠哮喘模型中密质骨间充质干细胞对慢性气道重塑的抑制作用
2014/05/07
摘要
除疫苗和药物治疗外,哮喘治疗仍需要新的治疗策略。在新的治疗方法的发展方面,间充质干细胞(MSCs)在再生医学中具有前景。密质骨(CB)MSCs是治疗肺损伤性慢性哮喘的一种替代疗法。本研究旨在从具有再生能力的鼠CB中分离出高浓缩的MSCs,研究这些细胞对卵清蛋白诱导的慢性哮喘鼠模型的气道重塑和炎症的作用。mCB-MSCs被分离,表征,GFP标记,然后注入到卵清蛋白(OVA)诱导的慢性哮喘鼠中。组织病理学改变包括基底膜、上皮细胞、上皮下平滑肌厚度和杯状细胞增生,以及评估肺组织中的MSCs迁移。与PBS组相比,卵清蛋白诱导组组织病理学改变增加(P<0.001)。注入mCB-MSC显著降低近端、远端气道组织病理学改变(P<0.001)。我们发现静脉诱导后2周,GFP标记的MSCs位于OVA组的肺中。而且,mCB-MSCs也显著提高卵清蛋白诱导鼠(OVA+MSC 组)的T细胞应答(P<0.037)。我们的研究表明,mCB-MSCs迁移至肺组织,抑制鼠哮喘动物模型中的组织病理学改变。研究结果证明,mCB-MSCs可能是治疗慢性哮喘炎症和重构的一种替代疗法。
(苏楠 审校)
Int Immunopharmacol. 2014 Mar 5. pii: S1567-5769(14)00082-4. doi: 10.1016/j. intimp. 2014.02.028. [Epub ahead of print]
Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.
Ogulur I1, Gurhan G1, Aksoy A2, Duruksu G2, Inci C2, Filinte D3, Kombak FE3, Karaoz E2, Akkoc T4.
Abstract
New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P<0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P<0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (P<0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma.
Int Immunopharmacol. 2014 Mar 5. pii: S1567-5769(14)00082-4. doi: 10.1016/j. intimp. 2014.02.028. [Epub ahead of print]
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学龄期儿童哮喘对气道致病菌异常的免疫反应与婴儿期一致
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脂肪酸、炎症和哮喘