人骨髓间充质干细胞治疗急性哮喘小鼠模型气道炎症的频率评价
2021/01/28
摘要
背景:过敏性哮喘实验模型研究表明，间充质干细胞(MSCs)对TH2细胞介导的炎症有治疗潜力。然而，这些治疗作用的机制尚不完全清楚，其安全性也未得到证实。
方法:我们以实验性哮喘小鼠模型为研究对象，根据治疗频率和时间分别研究了人脂肪源性间充质干细胞(hADSCs)和人骨髓源性间充质干细胞(hBMSCs)的疗效。
结果:卵清蛋白(OVA)致敏和激发小鼠表现出气道高反应性(AHR)、气道炎症和TH2细胞因子水平显著升高。双重和单个人间充质干细胞(hMSC)治疗均可显著降低AHR和支气管肺泡灌洗液计数。此外，hMSCs单次治疗可显著降低过敏性气道炎症。然而，在OVA致敏和激发过程中，hMSCs的双重处理进一步增加了炎症细胞浸润和TH2细胞因子水平。
结论:用hADSCs或hBMSCs治疗的结果抑制AHR和气道炎症。然而，双hMSC治疗可显著诱导嗜酸性气道炎症和肺组织学改变。因此，双剂量hMSC治疗哮喘无效，单次注射频率对哮喘的治疗显得更为重要。这些结果提示，hMSC疗法可以用于哮喘患者的治疗，但应谨慎使用。
Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma
Hur J, Kang JY, Kim YK, et al.
Abstract：
BACKGROUND: Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed.
METHODS:Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing.
RESULTS: Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels.
CONCLUSION:The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.
背景:过敏性哮喘实验模型研究表明，间充质干细胞(MSCs)对TH2细胞介导的炎症有治疗潜力。然而，这些治疗作用的机制尚不完全清楚，其安全性也未得到证实。
方法:我们以实验性哮喘小鼠模型为研究对象，根据治疗频率和时间分别研究了人脂肪源性间充质干细胞(hADSCs)和人骨髓源性间充质干细胞(hBMSCs)的疗效。
结果:卵清蛋白(OVA)致敏和激发小鼠表现出气道高反应性(AHR)、气道炎症和TH2细胞因子水平显著升高。双重和单个人间充质干细胞(hMSC)治疗均可显著降低AHR和支气管肺泡灌洗液计数。此外，hMSCs单次治疗可显著降低过敏性气道炎症。然而，在OVA致敏和激发过程中，hMSCs的双重处理进一步增加了炎症细胞浸润和TH2细胞因子水平。
结论:用hADSCs或hBMSCs治疗的结果抑制AHR和气道炎症。然而，双hMSC治疗可显著诱导嗜酸性气道炎症和肺组织学改变。因此，双剂量hMSC治疗哮喘无效，单次注射频率对哮喘的治疗显得更为重要。这些结果提示，hMSC疗法可以用于哮喘患者的治疗，但应谨慎使用。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Journal of Korean Medical Science, 2020, 35(23). e188）
（Journal of Korean Medical Science, 2020, 35(23). e188）
Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma
Hur J, Kang JY, Kim YK, et al.
Abstract：
BACKGROUND: Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed.
METHODS:Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing.
RESULTS: Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels.
CONCLUSION:The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.
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间充质干细胞通过Wnt /β-catenin信号通路减少哮喘大鼠肺中的气道重塑
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支气管热成形术与美泊利单抗：在严重哮喘门诊的结局比较
