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<p>Considering the increasing prevalence of pulmonary fibrosis (PF) and the increased exposure to risk factors contributing to its development, this study utilizes the bleomycin (BLM)-induced PF model to explore the potential early therapeutic strategies displayed by the bone marrow mesenchymal stem cells (BMMSCs) and their derived exosomes. The research assessed the efficacy of two administration methods: injection and inhalation by employing a comprehensive evaluation approach, including computed tomography imaging, biochemical assays, molecular analysis, and histopathological examinations. Fifty Wistar rats were divided into 5 groups; the CON group received saline intratracheally (IT) and served as the control group, the BLM group received IT BLM (5&#xa0;mg/kg), the BMMSCs group received (BLM + BMMSCs in a dose of 10<sup>6</sup> cells per rat, I/P), the Exo-INJ group received (BLM + BMMSCs-derived exosomes 100&#xa0;µg per rat I/P), and the Exo-INH group received (BLM + BMMSCs-derived exosomes 100&#xa0;µg by inhalation). The oxidative status indicators, glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and the level of surfactant protein D (SP-D), a biomarker of lung damage, were evaluated. Furthermore, the level of genetic expression of inflammatory cytokines interleukin-10 (<i>Il10</i>), interleukin-1&#xa0;beta (<i>Il1b</i>), pro-fibrotic and apoptotic markers, such as transforming growth factor-beta (<i>Tgfb</i>), Bcl-2-Associated X Protein (<i>Bax</i>), and fibroblast growth factor 2 (<i>Fgf2)</i>, which functions as a growth factor to protect lung epithelial damage, were determined. Both BMMSCs and their derived exosomes exhibited antioxidant, anti-inflammatory, and regenerative properties and have early therapeutic effects against PF, underlining them as promising antifibrotic candidates. In addition, the inhalation approach demonstrated superior performance in a specific metric while yielding comparable results in another. Consequently, it cannot be regarded as the optimal strategy across all evaluation criteria. Therefore, more studies are required to substantiate its applicability and explore the potential improvement that could enhance its overall efficacy.</p>

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Targeting early pulmonary fibrosis with bone marrow mesenchymal stem cells and their derived exosomes: a comparative study of inhalation versus injection delivery in bleomycin-induced rat lung injury

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Meral Hakam,
  • Ismail Mostafa,
  • Eman I. Hassanen,
  • Hamdy Rizk,
  • Marwa A. Ibrahim,
  • Ghada E. Ali

摘要

Considering the increasing prevalence of pulmonary fibrosis (PF) and the increased exposure to risk factors contributing to its development, this study utilizes the bleomycin (BLM)-induced PF model to explore the potential early therapeutic strategies displayed by the bone marrow mesenchymal stem cells (BMMSCs) and their derived exosomes. The research assessed the efficacy of two administration methods: injection and inhalation by employing a comprehensive evaluation approach, including computed tomography imaging, biochemical assays, molecular analysis, and histopathological examinations. Fifty Wistar rats were divided into 5 groups; the CON group received saline intratracheally (IT) and served as the control group, the BLM group received IT BLM (5 mg/kg), the BMMSCs group received (BLM + BMMSCs in a dose of 106 cells per rat, I/P), the Exo-INJ group received (BLM + BMMSCs-derived exosomes 100 µg per rat I/P), and the Exo-INH group received (BLM + BMMSCs-derived exosomes 100 µg by inhalation). The oxidative status indicators, glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and the level of surfactant protein D (SP-D), a biomarker of lung damage, were evaluated. Furthermore, the level of genetic expression of inflammatory cytokines interleukin-10 (Il10), interleukin-1 beta (Il1b), pro-fibrotic and apoptotic markers, such as transforming growth factor-beta (Tgfb), Bcl-2-Associated X Protein (Bax), and fibroblast growth factor 2 (Fgf2), which functions as a growth factor to protect lung epithelial damage, were determined. Both BMMSCs and their derived exosomes exhibited antioxidant, anti-inflammatory, and regenerative properties and have early therapeutic effects against PF, underlining them as promising antifibrotic candidates. In addition, the inhalation approach demonstrated superior performance in a specific metric while yielding comparable results in another. Consequently, it cannot be regarded as the optimal strategy across all evaluation criteria. Therefore, more studies are required to substantiate its applicability and explore the potential improvement that could enhance its overall efficacy.