Department of Pediatrics, Nephrology, Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Respiratory, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8137-8145. doi: 10.3892/mmr.2017.7605. Epub 2017 Sep 25.
Mesenchymal stem cells (MSCs) possess reparative and immunoregulatory properties, representing a hope for stem cell‑based treatments. However, the mechanisms by which transplanted MSCs affect T helper (Th)17/regulatory T cell (Treg) balance in asthma patients remain unclear. The aim of the present study was to assess the therapeutic effects of human placenta MSCs (hPMSCs) in asthma, and explore the underlying mechanisms; in addition, the impact of hPMSCs transplantation on Th17/Treg balance in lymph and serum samples from asthmatic animals was evaluated. Sprague‑Dawley rats were sensitized and challenged with ovalbumin (OVA). Administration of hPMSCs from human placenta resulted in increased Th17 and Treg in lymph samples compared with peripheral blood specimens. Enhanced pause values in OVA‑treated animals were significantly higher than those in the control and hPMSCs treatment groups. The numbers of total cells, macrophages, neutrophils, and eosinophils were markedly increased in the OVA group compared with those of control + hPMSCs and control groups. In addition, interleukin 10, forkhead box P3 (Foxp3) and Treg levels in lymph, peripheral blood and lung tissue samples from asthma rats were increased significantly following hPMSC transplantation. Furthermore, Foxp3 protein levels increased, while those of RAR‑related orphan receptor γ (RORγt) decreased after hPMSCs transplantation compared with the asthma group. Reduced IL‑17, RORγt and Th17 levels were accompanied by reduced inflammatory cell infiltration, sub‑epithelial smooth layer attenuation and mucus production in lung tissues. These results suggest that hPMSCs may improve airway hyperresponsiveness and inflammation by regulating the Th17/Treg balance in rats with asthma.
间充质干细胞（MSCs）具有修复和免疫调节特性，代表了基于干细胞治疗的希望。然而，移植的 MSCs 如何影响哮喘患者的辅助性 T 细胞（Th）17/调节性 T 细胞（Treg）平衡尚不清楚。本研究旨在评估人胎盘间充质干细胞（hPMSCs）在哮喘中的治疗作用，并探讨其潜在机制；此外，还评估了 hPMSCs 移植对哮喘动物淋巴和血清样本中 Th17/Treg 平衡的影响。将 Sprague-Dawley 大鼠用卵清蛋白（OVA）致敏和攻击。与外周血标本相比，hPMSCs 来自人胎盘的给药导致淋巴样本中 Th17 和 Treg 增加。与对照组和 hPMSCs 治疗组相比，OVA 处理动物的增强暂停值显着升高。与对照+ hPMSCs 组和对照组相比，OVA 组的总细胞、巨噬细胞、中性粒细胞和嗜酸性粒细胞数量明显增加。此外，哮喘大鼠淋巴、外周血和肺组织样本中的白细胞介素 10、叉头框 P3（Foxp3）和 Treg 水平在 hPMSC 移植后显着增加。此外，与哮喘组相比，hPMSCs 移植后 Foxp3 蛋白水平增加，而 RAR-相关孤儿受体 γ（RORγt）水平降低。IL-17、RORγt 和 Th17 水平降低伴随着肺组织中炎症细胞浸润、亚上皮平滑肌层衰减和粘液产生减少。这些结果表明，hPMSCs 通过调节哮喘大鼠的 Th17/Treg 平衡，可能改善气道高反应性和炎症。
