Effects of Mesenchymal Stem Cells and Their Derived Microvesicles on Pulmonary Toxicity Induced by Petrol Exhaust Nanoparticle; Histological and Immuno-Histochemical Study

ABSTRACT

Background: Diesel vehicles exhaust contains toxic nanoparticles that drastically affect lung tissue due to their direct cytotoxic effects, induction of oxidative stress, inflammatory signaling pathways and DNA damage. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory effects and efficient regenerative capacity in chronic lung diseases. Objectives: Evaluation of the effects of MSCs and MSCs-derived micro vesicles (MSCs-MVs) on pulmonary toxicity induced by diesel exhaust nanoparticles (DENPs). Materials and Methods: Sixty male rats were equally divided into Group I (Control rats), Group II (DENPs group) received repeated doses of DENPs (180μg/rat) intratracheally every other day for 6 days, Group III (MSCs group) received MSCs intravenously (3×106 cells) after the last dose of DENPs and Group IV (MSCs-MVs group) received MSCs-MVs (0.5 mg/mL) intravenously after the last dose of DENPs. Lung tissue were subjected to histological and immunohistochemical assessment. Inflammatory cytokines and bronchoalveolar lavage fluid (BALF) contents of inflammatory cells, albumin, LDH and total proteins were evaluated. Results: Histological picture of lung tissue in DENPs group showed numerous collapsed alveoli, thick interalveolar septa and marked cellular infiltration. Elastic fibers were markedly decreased by DENPs. Increased optical density of NF-κB/p65 immunoreactivity. Bronchoalveolar lavage fluid showed significant elevation of inflammatory cytokines (TNF-a, IL-6), polymorphonuclear leukocytes (PMN), neutrophils, macrophages, LDH, total proteins and albumin. Treatment with either MSCs or MSCs-MVs led to a significant amelioration of all of the aforementioned studied parameters. Conclusion: MSCs-MVs and MSCs showed significant therapeutic effects against DENPs damaging effects on the lung tissues via their regenerative capacity and anti-inflammatory effects.