Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul, 06591, Republic of Korea.
Sci Rep. 2022 Jul 14;12(1):12032. doi: 10.1038/s41598-022-16165-8.
It is challenging to overcome difficult-to-treat asthma, and cell-based therapies are attracting increasing interest. We assessed the effects of mesenchymal stem cell (MSC) treatments using a murine model of chronic ovalbumin (OVA)-challenged asthma. We developed a murine model of chronic allergic asthma using OVA sensitization and challenge. Human adipose-derived MSCs (hADSCs) or human bone marrow-derived MSCs (hBMSCs) were administered. We measured the levels of resistin-like molecule-β (RELM-β). We also measured RELM-β in asthma patients and normal controls. OVA-challenged mice exhibited increased airway hyper-responsiveness, inflammation, and remodeling. hBMSC treatment remarkably decreased airway hyper-responsiveness but hADSC treatment did not. Both MSCs alleviated airway inflammation, but hBMSCs tended to have a more significant effect. hBMSC treatment reduced Th2-cytokine levels but hADSC treatment did not. Both treatments reduced airway remodeling. The RELM-β level decreased in the OVA-challenged control group, but increased in both treatment groups. We found that the serum level of RELM-β was lower in asthma patients than controls. MSC treatments alleviated the airway inflammation, hyper-responsiveness, and remodeling associated with chronic asthma. hBMSCs were more effective than hADSCs. The RELM-β levels increased in both treatment groups; the RELM-β level may serve as a biomarker of MSC treatment efficacy.
治疗难治性哮喘具有挑战性,细胞疗法越来越受到关注。我们使用慢性卵清蛋白(OVA)挑战哮喘的小鼠模型评估间充质干细胞(MSC)治疗的效果。我们使用 OVA 致敏和挑战建立了慢性变应性哮喘的小鼠模型。给予人脂肪来源的间充质干细胞(hADSCs)或人骨髓来源的间充质干细胞(hBMSCs)。我们测量了抵抗素样分子-β(RELM-β)的水平。我们还测量了哮喘患者和正常对照者的 RELM-β。OVA 挑战的小鼠表现出气道高反应性、炎症和重塑增加。hBMSC 治疗显著降低气道高反应性,但 hADSC 治疗没有。两种 MSC 均减轻气道炎症,但 hBMSC 倾向于具有更显著的效果。hBMSC 治疗降低 Th2 细胞因子水平,但 hADSC 治疗没有。两种治疗均减轻气道重塑。OVA 挑战对照组的 RELM-β 水平降低,但在两个治疗组中均增加。我们发现哮喘患者的血清 RELM-β 水平低于对照组。MSC 治疗减轻与慢性哮喘相关的气道炎症、高反应性和重塑。hBMSCs 比 hADSCs 更有效。两个治疗组的 RELM-β 水平均升高;RELM-β 水平可能是 MSC 治疗效果的生物标志物。