Histological Study on Possible Therapeutic Effect of BM-MSCs on Healing of Lung Fibrosis Induced by CCl 4 with Reference to Macrophage Plasticity

Abstract

Background: Lungs are susceptible to several types of toxins. Macrophages may play role in lung fibrosis. Mesenchymal stem cells (MSCs) have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine. Objectives: Investigate possible therapeutic effects of bone marrow (BM)-MSCs on lung injury induced by carbon tetrachloride (CCl4) in adult rats with reference to role of macrophages plasticity. Material and methods: Forty-five adult male albino Wistar rats were divided into four groups. Group I (control). Group II (CCl4): rats received intraperitoneal injection of CCl4 (0.1 ml/100 g body weight) twice weekly for two weeks. Group III (BM-MSCs treated) received single injection of BM-MSCs after last injection of CCl4 and were left for further two weeks. Group IV (recovery): were left for two weeks after last injection of CCl4. At the end of experiment, all rats were sacrificed. Lung specimens were processed and subjected to H&E, Mallory`s trichrome, CD68, toluidine blue, transmission electron microscope and histomorphometric and statistical studies. Results: CCl4 and recovery groups showed thickening of interalveolar septa with mononuclear cellular infiltration, dissolved lamellar bodies in pneumocytes type-II and appearance of foamy macrophages. Significant increase in mean area percentage of collagen fibers, and mean number of CD68 macrophages were also noticed. BM-MSCs improved these histological changes with a significant increase number in pneumocyte type-II. Conclusions: CCl4 caused lung injury that was associated with inflammation, increased number of macrophages, and collagen fiber deposition. Treatment with BM-MSCs alleviates these changes and could be used in regenerative medicine.