Therapeutic Efficacy of Adipose-Derived Stem Cells for Bleomycin-Induced Idiopathic Pulmonary Fibrosis

Objective: To compare the therapeutic effects of intravenous (IV) and intratracheal (IT) delivery of adipose-derived stem cells (ADSCs) in a mouse model of bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF). Materials and Methods: In this experimental study, BALB/c mice were divided into 4 groups: control, BLM only, BLM+ADSC(IV), BLM+ADSC(IT). ADSCs were administered on day 14 after BLM induction. Outcomes measured on day 42 included mortality, body weight, lung edema, collagen deposition, fibrosis scoring, cytokine levels (TGF-β, SDF-1, IL-6, IL-1β, TNF-α), hydroxyproline, and leukocyte infiltration. Results: ADSC(IT) reduced mortality more effectively than ADSC(IV). Both IV and IT mitigated weight loss and lung edema with no significant difference. Both routes significantly decreased collagen synthesis, collagen fiber accumulation, Ashcroft scores, and hydroxyproline levels. Both routes lowered TGF-β, α-SMA, TNF-α, IL-6, IL-1β, and SDF-1 levels, and reduced leukocyte infiltration and alveolar barrier dysfunction, with no significant difference between routes. Conclusion: This design enables discrimination between route-dependent and route-independent therapeutic effects of ADSCs, thereby providing new insight into the optimization of stem cell delivery strategies for pulmo nary fibrosis. Importantly, whether the choice of delivery route differentially affects survival and inflammatory resolution, independent of antifibrotic efficacy, remains insufficiently addressed in current preclinical studies.