Department of Respiratory, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Respiratory, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
J Investig Med. 2023 Mar;71(3):235-243. doi: 10.1177/10815589221140590.
Asthma is a complex respiratory disease, which is controlled by genetic and environmental factors. Type 2-dominant immune response is responsible for asthma. Decorin (Dcn) and stem cells have modulatory effect on immune system and may control tissue remodeling and asthma pathophysiology. In this study, immunomodulatory effect of transduced induced pluripotent stem cells (iPSCs) with expression of gene on allergic asthma pathophysiology was evaluated. After transduction of iPSCs with gene, allergic asthma mice were treated with iPSCs and transduced iPSCs via intrabronchial. Then, airway hyperresponsiveness (AHR), levels of interleukin (IL)-4, IL-5, IL-13, IL-33, total IgE, leukotrienes (LTs) B4, C4, hydroxyproline (HP) content, and transforming growth factor-beta (TGF-β) were measured. Also, lung histopathology study was done. AHR, levels of IL-4, IL-5, IL-13, IL-33, total IgE, LTs B4, C4, TGF-β, HP content, mucus secretion, goblet cell hyperplasia, and eosinophilic inflammation were controlled by iPSCs and transduced iPSCs treatment. Therapeutic effect of iPSCs could control main allergic asthma symptoms and related pathophysiologic mechanisms and the effect can be increased when applied with expression gene.
哮喘是一种复杂的呼吸道疾病,由遗传和环境因素控制。2 型主导的免疫反应是导致哮喘的原因。核心蛋白聚糖(Dcn)和干细胞对免疫系统具有调节作用,可能控制组织重塑和哮喘病理生理学。在这项研究中,评估了表达基因的转导诱导多能干细胞(iPSCs)对过敏性哮喘病理生理学的免疫调节作用。用基因转导 iPSCs 后,通过支气管内途径用 iPSCs 和转导 iPSCs 治疗过敏性哮喘小鼠。然后,测量气道高反应性(AHR)、白细胞介素(IL)-4、IL-5、IL-13、IL-33、总 IgE、白三烯(LT)B4、C4、羟脯氨酸(HP)含量和转化生长因子-β(TGF-β)。此外,还进行了肺组织病理学研究。iPSCs 和转导 iPSCs 治疗可控制 AHR、IL-4、IL-5、IL-13、IL-33、总 IgE、LTs B4、C4、TGF-β、HP 含量、黏液分泌、杯状细胞增生和嗜酸性粒细胞炎症等主要过敏性哮喘症状和相关病理生理机制。当应用基因表达时,iPSCs 的治疗效果可以控制主要的过敏性哮喘症状和相关的病理生理机制,并且可以增加这种效果。