The Therapeutic Potential of Bone Marrow-Derived Mesenchymal Stem Cells Versus their Extracellular Vesicles on A Rat Model of Pulmonary Alveolar Injury. Histological, Biochemical and Physiological Study

Document Type : Original Article

Authors

1 Histology and cell biology, Alexandria faculty of medicine

2 Medical Biochemistry, Alexandria faculty of medicine

3 Medical physiology, Alexandria faculty of medicine

4 Human Anatomy and Embryology, Alexandria faculty of Medicine

5 Alexandria faculty of medicine, histology and cell biology departement

Abstract

Introduction: Pulmonary alveolar injury can eventually result in pulmonary fibrosis, nevertheless, only palliative treatment is available. Bone marrow-derived mesenchymal stem cells (BM-MSCs) and their extracellular vesicles (EVs) possess antifibrotic effects.
Aim of the Work: To assess the therapeutic potential of BM-MSCs versus their EVs on bleomycin model of pulmonary alveolar injury.
Materials and Methods: 66 adult rats were used; 60 female rats for experimental groups and 6 male rats for obtainment of BM-MSCs. BM-MSCs and their derived EVs were characterized. The 60 rats were randomized equally into: control group, and other 4 groups received intratracheal instillation of bleomycin. On day 14, the rats were either sacrificed (fibrosis group; FG) or received free culture media (spontaneous recovery group; SRG); BM-MSCs (SCG) or EVs (EVG), respectively. Pulmonary function tests (PFTs) and arterial blood gases (ABG) were evaluated at the beginning and at the end of the experiment. On day 28, the body weights were recorded and the rats were sacrificed. The lungs were obtained and weighed and lung to body weight (LW/BW) were calculated. The tissue levels of transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor (VEGF), Bcl-2 Associated X-protein (BAX), malondialdehyde (MDA), the antioxidant superoxide dismutase and total antioxidant capacity were measured. The lungs were processed for light and electron microscopic examination. The thickness of the interalveolar septa and percentage area of collagen were subjected to morphometric analysis. Statistical analysis was done.
Results: Bleomycin resulted in distorted alveoli, nuclear changes affecting the alveolar cells with vacuolation, proliferation of type II pneumocytes, desquamated cells, cellular infiltration and congested blood vessels, significant increase in collagen deposition, thickness of septa, LW/BW, TGF-β, VEGF, BAX and MDA with reduction in PFTs and antioxidant enzymes with disturbed ABG. EVG revealed moderate improvement, while SCG showed better results.
Conclusion: BM-MSCs injection showed superb antifibrotic effect compared to their derived EVs.

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