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)

Document Type : Large Animal Health Management

Authors

1 1Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

3 2Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran 3Institute of Biomedical Research, University of Tehran, Tehran, Iran

4 4Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

5 6Health Management Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran

6 7 Student of Veterinary Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract

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.

Keywords


Amrine, D. E., White, B. J., Larson, R., Anderson, D. E., Mosier, D. A., Cernicchiaro, N. (2013) Precision and accuracy of clinical illness scores, compared with pulmonary consolidation scores, in Holstein calves with experimentally induced Mycoplasma bovis pneumonia. Am J Vet Res. 74: 310-315.##
Abraham, E. (2003) Neutrophils and acute lung injury. Crit Care Med. 31: S195-S199.
Asmussen, S., Ito, H., Traber, D. L., Lee, J. W., Cox, R. A., Hawkins, H. K., Enkhbaatar, P. (2014) Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax. 69: 819-825. ##
Devaney, J., Horie, S., Masterson, C., Elliman, S., Barry, F., O’Brien, T., Laffey, J. G. (2015) Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax.70: 1468-3296.##
Doyonnas, R., LaBarge, M. A., Sacco, A., Charlton, C., Blau, H. M. (2004) Hematopoietic contribution to skeletal muscle regeneration by myelomonocytic precursors. Proc Natl Acad Sci USA. 101: 13507-12.##
Gupta, N., Su, X., Popov, B., Lee, J. W., Serikov, V., Matthay, M. A. (2012) Intra-pulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 179: 1855-1563.##
Krasnodembskaya, A., Song, Y., Fang, X., Gupta, N., Serikov, V., Lee, J. W., Matthay, M. A. (2010) Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37. Stem Cells. 28: 2229-2238. ##
Kwak, H. J., So, J. N., Lee, S. J., Kim, I., Koh, G. Y. (1999) Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett. 448: 249-253.##
Lee, J. W., Fang X. Fau., Gupta, N., Serikov, V., Matthay, M. A. (2009) Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci USA. 106: 16357-16362.##
Mei, S. H. J., McCarter, S. D., Deng, Y., Parker, C. H., Liles, W. C., Stewart, D. J. (2007) Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 4: 1525-1537.##
Moodley, Y., Sturm, M., Shaw, K., Shimbori, C., Tan, D. B., Kolb, M., Graham, R. (2016) Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury.Stem Cell Res. 17: 25-31.##
Mokhber Dezfouli, M. R., Sadeghian Chaleshtori, S., Dehghan, M. M., Tavanaeimanesh, H., Baharvand, H., Tahamtani, Y. (2017) The therapeutic potential of differentiated lung cells from embryonic stem cells in lung diseases. Cur Stem Cell Res & Ther. 12: 80-84.##
Mokhber Dezfouli, M. R., Lotfollahzadeh, S., Heidari Sureshjani, M., Dehghan, M. M., Nikbakht, Gh. R., Eftekhari, Z., Tavanaeimanesh, H., Sadeghian Chaleshtori, S., Jani, M., Arab Yarmohammadi, M. (2017) Changes in clinical signs after treatment in calves with experimental colisepticemia with Escherichia coli. J Vet Res. 72: 63-71.##
Ortiz, L., Dutreil, M., Fattman, C., Pandey, A. C., Torres, G., Go, K., Phinney, D. G. (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA. 104: 11002-11007. ##
Pizurki, L., Zhou, Z., Glynos, K., Roussos, C., Papapetropoulos, A. (2003) Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Br J Pharmacol. 139: 329-336##
Radostits, O. M., Gay, C. C., Hinchcliff, K. W., Constable, P. D. (2007) Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats. (10th ed.) Elsevier Health Sciences, Philadelphia, USA. p. 847-89.##
Rojas, M., Xu J., Woods, C. R., Mora, A. L., Spears, W., Roman, J., Brigham, K. L. (2005) Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 33: 1445-152. ##
Mauricio, R., Nayra, C., Ergin, K., John, R. T., Eder, C., Robert, D., Anthony, T., Christian, B. (2014) Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep . Stem Cell Res & Ther. 5: 42-55.##
Rubenfeld, G. D., Caldwell, E., Peabody, E., Weaver, J., Martin, D. P., Neff, M., Hudson, L. D. (2005) Incidence and outcomes of acute lung injury. New England Journal of Medicine. 353: 1685-1693.##
Sadeghian Chaleshtori, S.,  Mokhber Dezfouli, M. R., Dehghan, M. M., Tavanaeimanesh, H. (2016) Generation of Lung and Airway Epithelial Cells from Embryonic Stem Cells In Vitro. Criti Rev in Eukar Gene Expr. 26: 1-9.##
Tagami, T., Kushimoto, S., Tosa, R., Omura, M., Yonezawa, K., Akiyama, G., Hirama, H., Yokota, H. (2011) Plasma neutrophil elastase correlates with pulmonary vascular permeability: a prospective observational study in patients with pneumonia. Respiro. 16: 953-958. ##
Volk, S. W., Theoret, C. (2013) Translating stem cell therapies: the role of companion animals in regenerative medicine. ound Repa Regen. 21: 382-394.##
Xu, J., Woods, C., Mora, A. L., Mora, A., Joodi, R., Brigham, K. L., Iyer, S., Rojas, M. (2007) Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Ame J Physiol Lung Cell Mol Physiol. 293: 131-141.##