Improvement of Clinical Signs in Experimental Model of Acute Respiratory Distress Syndrome (ARDS) in Sheep Following Autograft of Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs)

Background: ARDS is a lung disorder that causes death in human and livestock and new therapeutic approaches such as stem cell therapy are essential because of lack of specific drug therapies for it. Objectives: Evaluation of the therapeutic effects of intrapulmonary transplantation of BM-MSCs to improvement of clinical signs in experimental model of ARDS created by lipopolysaccharide(LPS)E.Coli strains-O55:B5 in sheep is the aim of this study. Methods: In this study, 10 male sheep 3-4 months old Shall were used after random placement into two groups, treatment and control. Of sheep in the treatment group after anesthesia with ketamine and xylazine collected bone marrow samples and in the clean room BM-MSCs isolated, amplified and were identified with the evaluation of surface markers. Then experimental model of ARDS was induced by endotracheal injection of LPS to dose 400μg/kg. Clinical signs and radiograph images performed before and 24 hours after injection of LPS. After confirming inflammation, the sheep were anesthetized and on sternal position 50×106 cells of BM-MSCs third passage were transferred in treatment group as autograft by the catheter lavage in the bifurcation of the trachea and PBS in control group. Then clinical signs were recorded at hours of 3,6and 12 and on days 1,2,3 and 7 in both groups and finally, were analyzed based on the scored system. Results: The data showed transplantation of BM-MSCs caused significant improvement in clinical signs including heart rate, respiratory rate, body temperature, respiratory sounds, cough, mucosal status, nasal secretions, appetite and physical condition compared with control group. A significant decrease in respiratory rate and body temperature from 12 hours and in heart rate from 24 hours to next be began. Also, changes in breath sounds on the first day after transplantation, physical condition, mucous membranes and appetite on the third day, the occurrence of cough and abnormal discharge from the nose on the seventh day had returned to pre-inflammation (-24 time) and the median of score was zero for them. Conclusions: This study showed that transplantation of BM-MSCs can cause improves and the reduction in the severity of the clinical signs of ARDS, significantly.