Role of Mesenchymal Stem Cells Exosomes in Lipopolysaccharide-induced Acute Lung Injury in Rats, a histological study

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the leading cause of death in severe COVID-19 cases since 2019. Mesenchymal stem cells (MSCs) and their exosomes have shown potential in modulating inflammation. In experimental animals, lipopolysaccharide (LPS), could induce ALI, mimicking ARDS in humans.Aim: Histological assessment of the role of exosomes derived from bone marrow MSCs in treatment of LPS-induced acute lung injury model in adult male albino rats.Materials & Methods: Thirty-five rats were used. Five young albino rats were sacrificed to extract bone marrow-derived MSCs and their exosomes. The remaining 30 adult rats were divided into: Group I (Control): No treatment. Group II (LPS group): Received a single intraperitoneal LPS injection (6 mg/kg). Group III (LPS + Exosomes group): Received LPS like Group II, then an intravenous exosome injection (30 µL/rat) one hour later. After 24 hours, lung samples were analyzed using microscopy, morphometric, and statistical methods.Results: H&E-stained sections of Group II revealed marked inflammatory changes with thickened interalveolar septa. Many alveoli appeared collapsed, others dilated with destructed walls. Blood vessels were congested. The lining epithelium of bronchioles appeared occasionally desquamated. Masson’s Trichrome staining showed an increase of collagen fibers. Immunohistochemical stain showed a significant reaction to iNOS antibodies and a significant Caspase-3 immune reactivity. Examination with Transmission electron microscopy showed Type I Pneumocyte with nuclear and cytoplasmic changes, Type II pneumocytes with degenerated lamellar bodies and lost microvilli. Eosinophils and macrophages were infiltrating the interstitium. The lung structure in Group III showed significant improvement in all parameters. Conclusion: The study showed that MSC-exosomes could help in treatment of ALI caused by LPS in rats. This suggests that MSC-exosomes may have a potential role in treatment of ARDS.