Long-term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma.
Long-term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma.
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DOI：
10.1111/cea.12411
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Reinero CR
中科院分区：
文献类型：
--
作者：
Trzil JE;Masseau I;Webb TL;Chang CH;Dodam JR;Cohn LA;Liu H;Quimby JM;Dow SW;Reinero CR
间充质干细胞(MSCs)可减少急性哮喘模型小鼠的气道嗜酸性粒细胞增多、气道高反应性(AHR)和气道重塑。我们假设，在慢性猫哮喘模型中，间充质干细胞会减少这些标志性特征。记录同种异体脂肪来源的MSCs对气道炎症、气道高反应性(AHR)和随时间的重塑的影响，并研究MSCs改变慢性实验性猫过敏性哮喘局部和系统免疫反应的机制。在研究登记时，患有慢性实验性哮喘的猫接受了六次MSCs静脉注射(0.36-2.5X10E7 MSCs/输液)或安慰剂双月一次。猫在基线和纵向上进行了一年的评估。观察指标包括：支气管肺泡灌洗液细胞学以评估气道嗜酸性粒细胞增多；肺力学和临床评分以评估AHR；以及胸部计算机断层扫描(CT)以评估结构变化(气道重塑)。使用肺衰减(LA)和支气管壁增厚(BWT)评分系统对CT扫描进行评估。为了评估MSC的作用机制，进行了包括过敏原特异性IgE、细胞IL-10产生和过敏原特异性淋巴细胞增殖在内的免疫学检测。治疗组之间或随着时间的推移，在呼吸道嗜酸性粒细胞增多症或AHR方面没有差异。然而，在研究的第8个月，接受间充质干细胞治疗的动物的CT图像中的LA和BWT评分明显低于安慰剂治疗的猫(LAp=0.0311；BWT p=0.0489)。两组间的免疫学检测结果无明显差异。当在慢性过敏性猫科动物哮喘发生后给予MSCs时，MSCs未能减少呼吸道炎症和AHR。然而，在研究开始时重复使用MSCs确实在8个月时减少了气道重塑的CT测量，尽管这种效果在12个月时没有持续。有必要对MSC治疗进行进一步研究，包括重复使用MSC，以评估对慢性哮喘重塑的影响。
Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodeling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. To document effects of allogeneic, adipose-derived MSCs on airway inflammation, airway hyperresponsiveness (AHR), and remodeling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. Cats with chronic, experimentally-induced asthma received six intravenous infusions of MSCs (0.36–2.5X10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for one year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia; pulmonary mechanics and clinical scoring to assess AHR; and thoracic computed tomographic (CT) scans to assess structural changes (airway remodeling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA p=0.0311; BWT p=0.0489). No differences were noted between groups in the immunologic assays. When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodeling by month 8, though the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodeling in chronic asthma.
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影响因子：
168.9
作者：
Martinez, Fernando D.;Vercelli, Donata
通讯作者：
Vercelli, Donata
影响因子：
4
作者：
Ge, Xiahui;Bai, Chong;Chen, Ruohua
通讯作者：
Chen, Ruohua
影响因子：
4
作者：
Martinez-Gonzalez, Itziar;Cruz, Maria-Jesus;Aran, Josep M.
通讯作者：
Aran, Josep M.
DOI：
10.1152/ajplung.00182.2009
发表时间：
2010-12-01
影响因子：
4.9
作者：
Bonfield, Tracey L.;Koloze, Mary;Caplan, Arnold I.
通讯作者：
Caplan, Arnold I.
影响因子：
9.6
作者：
Busse, William W.
通讯作者：
Busse, William W.