Xu Jingran, Abudureheman Zulipikaer, Gong Hui, Zhong Xuemei, Xue Lexin, Zou Xiaoguang, Li Li
Department of Respiratory and Critical Care Medicine, First People's Hospital of Kashi, Kashi, China.
Clinical Research Center of Infectious Diseases (Pulmonary Tuberculosis), First People's Hospital of Kashi, Kashi, China.
Sci Rep. 2025 Aug 4;15(1):28339. doi: 10.1038/s41598-025-14286-4.
Pulmonary fibrosis (PF) is a progressive, irreversible disease with limited effective treatments. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have recently shown promise in PF therapy. This study evaluated the therapeutic effects and mechanisms of UC-MSCs combined with pirfenidone (PFD) in a bleomycin-induced PF model. C57BL/6 mice were divided into nine groups: control, model, PFD (100 mg/kg), UC-MSCs (0.5 × 10, 1.0 × 10, and 2.0 × 10 cells per animal), and PFD (100 mg/kg) + UC-MSCs (0.5 × 10, 1.0 × 10, and 2.0 × 10 cells per animal). The model was established by intratracheal bleomycin instillation. PFD was administered intraperitoneally twice daily from day 4 to 21 in the PFD and PFD + UC-MSCs groups, and UC-MSCs were injected via the tail vein on day 4 in the UC-MSCs and PFD + UC-MSCs groups. Outcomes included pulmonary function, histopathology, inflammatory factors (TGF-β1, INF-γ, IL-6) in serum, bronchoalveolar lavage fluid (BALF) and lung tissues, and markers of fibrosis (α-SMA, Collagen I) and collagen deposition. The results showed that the high-dose UC-MSCs group and the PFD + high-dose UC-MSCs group achieved the most significant improvements across all parameters compared to other groups (P < 0.05). The PFD + high-dose UC-MSCs group showed the most reduction in p-SMAD 2/3 levels (P < 0.05) and greater inhibition of pro-fibrotic gene expression. This suggests that the combined treatment effectively mitigates bleomycin-induced PF by inhibiting the TGF-β/SMAD pathway. High-dose UC-MSCs combined with PFD offers superior therapeutic effects for PF treatment.
肺纤维化（PF）是一种进行性、不可逆的疾病，有效治疗方法有限。人脐带间充质干细胞（UC-MSCs）最近在PF治疗中显示出前景。本研究评估了UC-MSCs联合吡非尼酮（PFD）在博莱霉素诱导的PF模型中的治疗效果及机制。将C57BL/6小鼠分为九组：对照组、模型组、PFD（100mg/kg）组、UC-MSCs组（每只动物0.5×10、1.0×10和2.0×10个细胞），以及PFD（100mg/kg）+UC-MSCs组（每只动物0.5×10、1.0×10和2.0×10个细胞）。通过气管内注入博莱霉素建立模型。在PFD组和PFD+UC-MSCs组中，从第4天至第21天每天腹腔注射PFD两次，在UC-MSCs组和PFD+UC-MSCs组中，于第4天经尾静脉注射UC-MSCs。观察指标包括肺功能、组织病理学、血清、支气管肺泡灌洗液（BALF）和肺组织中的炎症因子（TGF-β1、INF-γ、IL-6），以及纤维化标志物（α-SMA、I型胶原）和胶原沉积。结果显示，与其他组相比，高剂量UC-MSCs组和PFD+高剂量UC-MSCs组在所有参数上均取得了最显著的改善（P<0.05）。PFD+高剂量UC-MSCs组的p-SMAD 2/3水平降低最为明显（P<0.05），对促纤维化基因表达的抑制作用更强。这表明联合治疗通过抑制TGF-β/SMAD途径有效减轻了博莱霉素诱导的PF。高剂量UC-MSCs联合PFD对PF治疗具有更好的疗效。
