Pirfenidone combined with UC-MSCs reversed bleomycin-induced pulmonary fibrosis

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 × 10⁶, 1.0 × 10⁶, and 2.0 × 10⁶ cells per animal), and PFD (100 mg/kg) + UC-MSCs (0.5 × 10⁶, 1.0 × 10⁶, and 2.0 × 10⁶ 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.