Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model
Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model
复制标题
DOI：
10.1152/ajplung.00182.2009
复制
发表时间：
2010-12-01
影响因子：
4.9
通讯作者：
Caplan, Arnold I.
中科院分区：
文献类型：
--
作者：
Bonfield, Tracey L.;Koloze, Mary;Caplan, Arnold I.
Bonfield TL，Koloze M，Lennon DP，Zuchowski B，Yang SE，Caplan AI.人骨髓间充质干细胞抑制小鼠卵白蛋白哮喘模型的慢性气道炎症。Am J Physiol Lung Cell Mol Physiol 299：L760-L770，2010。首次发表于2010年9月3日; doi：10.1152/ajplung.00182.2009.-静脉内引入的同种异体人间充质干细胞（hMSC）可具有显著的抗炎活性，从而抑制移植物抗宿主病以及在这些疾病的人和动物模型中的中风、梗塞、脊髓损伤、半月板再生、腱炎、急性肾衰竭和心脏病的情况下的再生事件。hMSC产生生物活性因子，其为以下提供分子线索：1）T细胞的免疫抑制; 2）抗瘢痕形成; 3）血管生成; 4）抗凋亡;和5）再生（即，有丝分裂的宿主来源的祖细胞）。研究表明，hMSC对免疫系统具有深远的影响，并且在多发性硬化症和中风的免疫活性啮齿动物模型中具有良好的耐受性和治疗活性。此外，静脉内施用MSC导致肺定位。哮喘是一种主要的使人衰弱的肺部疾病，影响着世界上超过1.5亿人，不受控制的哮喘可能导致死亡。此外，哮喘相关疾病对儿童和成人的社会经济影响是数百万美元的医疗费用和工作日损失。hMSCs可能通过分泌生物活性因子或指导细胞活性为这种炎性肺病提供可行的多作用治疗。我们的研究显示了hMSCs在减少与哮喘的鼠卵清蛋白模型相关的慢性气道炎症方面的有效性和特异性。此外，这些研究的结果证实了hMSC在啮齿动物中的体内免疫有效性，并支持hMSC用于治疗与慢性哮喘相关的气道炎症的潜在治疗用途。
Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol 299: L760-L770, 2010. First published September 3, 2010; doi:10.1152/ajplung.00182.2009.-Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma.