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Abstract Lung fibrosis is a fatal and progressive lung disease that affects many patients worldwide. It is an end stage of many lung diseases. The main histopathological characteristic features of lung fibrosis are excessive deposition of extracellular matrix, accretion of fibroblasts, collapsing of alveoli and loss of normal lung architecture. Bleomycin (BLM) is a chemotherapeutic agent that is used widely in treatment of many malignancies as classical Hodgkin lymphoma, melanoma, ovarian carcinoma and testicular neoplasms. BLM administration is the gold standard method for developing lung fibrosis model. Bone marrow mesenchymal stem cells (BM-MSCs) are ideal for preclinical and clinical trials and are feasible. The aim of the present work was to assess the therapeutic potential of MSCs derived from bone marrow on bleomycin induced lung fibrosis in albino rats. The material & methods of this work included 35 Sprague Dawley (albino) rats, 5 males aged 2-3 weeks, weighed 27-32 g and 30 females, aged 6-8 weeks weighing 150-200 g. Male rats were used in this study for collecting the bone marrow mesenchymal stem cells, and thus to trace homing of these cells by QR-PCR. Female rats were classified into 2 groups; group I for optimization of lung fibrosis model that further subdivided to control group (group IA) and lung fibrosis induced group using itratracheal bleomycin in a single dose of 5mg/kg (group IB). Experimental group (group II) was randomly subdivided into group IIA; treated with BM-MSCs, group IIB; injected cell-free media in the tail vein. MSCs were isolated from bone marrow, characterized, cultured and passaged in vitro. All these procedures were conducted in stem cells laboratory in Center of Excellence for Research in Regenerative Medicine and its Application (CERRMA), Faculty of Medicine, Alexandria University. At third passage, once they became 70-80% confluent,BM- MSCs were injected in the tail vein in female rats of group IIA . Characterization of BM-MSCs was done by: 1. Daily examination of the morphology of cultured cells using phase contrast inverted microscopy. 2. Colony forming unit-fibroblast (CFU-F) assays. 3. Flow cytometric analysis of the cultured cells’ surface markers. Confirmation of lung fibrosis was done by measuring MRV, FVC &FEV1and histological examination using light and electron microscopes. Tissue lung sections stained with H&E of BLM treated rats demonstrated marked alterations of the structure of the lung in the form of collapsed alveoli, increased inter-alveolar septa and cellular infiltration.in addition, marked tissue congestion. |