Comparative Therapeutic Efficacy of Mesenchymal Stem Cell–Derived Microvesicles and Pumpkin Seed Oil as Drug Delivery Strategies in Bleomycin-Induced Pulmonary Fibrosis

Abstract

Background: Pumpkin seed oil (PSO) is a natural antioxidant with antifibrotic properties, while mesenchymal stem cell– derived microvesicles (MSC-MVs) promote tissue regeneration through bioactive signaling. This study aimed to improve therapeutic strategies for lung fibrosis by comparing the effects of PSO and MSC-MVs on bleomycin (BLM) -induced lung injury in rats to achieve better prognosis. Methods: Thirty-five adult male albino rats were housed under standard conditions and ethically used to study BLM - induced lung fibrosis. The rats were divided into control and experimental groups to evaluate the therapeutic effects of PSO and MSC-MVs. Lung fibrosis was induced by BLM, followed by treatment with PSO or MSC-MVs. Lung tissues were collected after 14 days to assess histological and immunohistochemical changes. Results: Quantitative and morphometric analyses demonstrated highly significant differences among the studied groups (P<0.001). BLM markedly increased serum malondialdehyde (MDA) and interleukin-6 (IL-6) levels, collagen fiber deposition, and alpha smooth muscle actin (α-SMA) expression, indicating severe inflammation and fibrosis with pronounced structural and ultrastructural lung damage. Treatment with PSO significantly reduced these parameters compared to the BLM group, though values remained higher than controls, reflecting partial protection. MSC-MVs produced the most pronounced therapeutic effect, significantly lowering MDA, IL-6, collagen deposition, and α-SMA expression to near-control levels and restoring lung architecture and ultrastructure. Conclusions: BLM administration successfully induced marked pulmonary fibrosis, as evidenced by significant increases in collagen deposition, α-SMA immunoreactivity, and serum MDA and IL-6 levels compared with controls.