Yıl: 2020 Cilt: 21 Sayı: 1 Sayfa Aralığı: 14 - 20 Metin Dili: İngilizce DOI: 10.5152/TurkThoracJ.2019.180136 İndeks Tarihi: 11-12-2020

Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats

Öz:
OBJECTIVES: Emphysema and chronic bronchitis have different pathophysiologies but both are significant components of chronic obstructive lung disease (COPD). The levels of Matrix metalloproteinase (MMP)-9 in the bronchoalveloar lavage fluid (BALF) and in serumindicate the presence of emphysema. Intratracheal administration of elastase has been used to create a rat model of emphysema. Adiposetissue-derived mesenchymal stem cells (MSC) have been postulated to prevent or reverse emphysema, however, this has not been examined in the rat model of elastase-induced emphysema.MATERIALS AND METHODS: In this study, 31 Wistar albino rats aged 6–8 weeks and weighing 250–300 g were assessed. On day 1, theanimals were treated intratracheally with 0.5 mL saline (control group, n=10), i.e., 0.5 mL saline solution containing 0.1 IU porcine pancreatic elastase (PPE) (Elastase group, n=12) or PPE plus MSC (Elastase-MSC group, n=9) was adminstered per animal. MSCs suspendedin serum were injected via the caudal vein on day 21. At least 106 cells were injected. All animals were sacrificed on day 42 and theemphysema index (EI) was calculated, along with measuring the BALF and serum MMP-9 concentrations.RESULTS: Porcine pancreatic elastase induced a significant degree of emphysema in the PPE groups as compared to the control group,which was determined by the EI index (p=0.008). This was not reversed by MSC treatment. The EI remained significantly low in comprison with the controls (p=0.001) and measured no different from the Elastase-treated animals. There was no statistically significantdifference between the BALF and serum MMP-9 levels between the control and treatment groups.CONCLUSION: Our findings suggest that therapeutic treatment with adipose tissue-derived MSC in rats has no effect on emphysema oron MMP9 expression, which is a known marker of emphysema.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD (Updated 2017). In; 2017.
  • 2. Kasahara Y, Tuder RM, Cool CD, et al. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med 2001;163(3 Pt 1):737-44. [CrossRef]
  • 3. Voelkel NF, Gomez-Arroyo J, Mizuno S. COPD/emphysema: The vascular story. Pulm Circ 2011;1:320-6. [CrossRef]
  • 4. Cheng SL, Lin CH, Yao CL. Mesenchymal Stem Cell Administration in Patients with Chronic Obstructive Pulmonary Disease: State of the Science. Stem Cells Int 2017;2017:8916570. [CrossRef]
  • 5. Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 2010;28:585- 96. [CrossRef]
  • 6. Zhen G, Liu H, Gu N, et al. Mesenchymal stem cells transplantation protects against rat pulmonary emphysema. Front Biosci 2008;13:3415-22. [CrossRef]
  • 7. Liu HM, Zhen GH, Zhang ZX, et al. Effects of bone marrow mesenchymal stem cells transplantation on the apoptosis of alveolar wall cells in papain and Co60-induced pulmonary emphysema rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2008;24:210-4.
  • 8. Wagner DE, Cardoso WV, Gilpin SE, et al. ATS Subcommittee on Stem Cells and Cell Therapies. An Official American Thoracic Society Workshop Report 2015. Stem Cells and Cell Therapies in Lung Biology and Diseases. Ann Am Thorac Soc 2016;13:S259-78. [CrossRef]
  • 9. Osiris. Osiris Therapeutics Reports interim data for COPD stem cell study 2009. In; 2012.
  • 10. Matthay MA, Thompson BT, Read EJ, et al. Therapeutic potential of mesenchymal stem cells for severe acute lung injury. Chest 2010;138:965-72. [CrossRef]
  • 11. Cho RJ, Kim YS, Kim JY, et al. Human adipose-derived mesenchymal stem cell spheroids improve recovery in a Mouse model of elastase-induced emphysema. BMB Rep 2017;50:79-84. [CrossRef]
  • 12. Baber SR, Deng W, Master RG, et al. Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol 2007;292:H1120-8. [CrossRef]
  • 13. Weiss DJ, Kolls JK, Ortiz LA, et al. Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 2008;5:637-67. [CrossRef]
  • 14. Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005;33:145-52. [CrossRef]
  • 15. van de Lest CH, Versteeg EM, Veerkamp JH, et al. Digestion of proteoglycans in porcine pancreatic elastase-induced emphysema in rats. Eur Respir J 1995;8:238-45. [CrossRef]
  • 16. Wang YH, Bai CX, Hong QY, et al. Anti-inflammatory effect of methoxyphenamine compound in rat model of chronic obstructive pulmonary disease. Acta Pharmacol Sin 2003;24:1324-7.
  • 17. Finsnes F, Skjonsberg OH, Tonnessen T, et al. Endothelin production and effects of endothelin antagonism during experimental airway inflammation. Am J Respir Crit Care Med 1997;155:1404-12. [CrossRef]
  • 18. Ishizawa K, Kubo H, Yamada M, et al. Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 2004;556:249-52. [CrossRef]
  • 19. Kawakami M, Matsuo Y, Yoshiura K, et al. Sequential and quantitative analysis of a murine model of elastase-induced emphysema. Biol Pharm Bull 2008;31:1434-8. [CrossRef]
  • 20. Luthje L, Raupach T, Michels H, et al. Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model. Respir Res 2009;10:7. [CrossRef]
  • 21. Gupta N, Su X, Popov B, et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007;179:1855-63. [CrossRef]
  • 22. Xu J, Woods CR, Mora AL, et al. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am J Physiol Lung Cell Mol Physiol 2007;293:L131-41. [CrossRef]
  • 23. Song L, Xu J, Qu J, et al. A therapeutic role for mesenchymal stem cells in acute lung injury independent of hypoxia-induced mitogenic factor. J Cell Mol Med 2012;16:376-85. [CrossRef]
  • 24. Zhen G, Xue Z, Zhao J, et al. Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells. Cytotherapy 2010;12:605-14. [CrossRef]
  • 25. Katsha AM, Ohkouchi S, Xin H, et al. Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol Ther 2011;19:196-203. [CrossRef]
  • 26. D'Agostino B, Sullo N, Siniscalco D, et al. Mesenchymal stem cell therapy for the treatment of chronic obstructive pulmonary disease. Expert Opin Biol Ther 2010;10:681-7. [CrossRef]
  • 27. Guan XJ, Song L, Han FF, et al. Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGFVEGF receptors. J Cell Biochem 2013;114:323-35. [CrossRef]
  • 28. Sun CK, Yen CH, Lin YC, et al. Autologous transplantation of adipose-derived mesenchymal stem cells markedly reduced acute ischemia-reperfusion lung injury in a rodent model. J Transl Med 2011;9:118.[CrossRef]
  • 29. Sammour I, Somashekar S, Huang J, et al. The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal HyperoxiaInduced Lung Injury. PloS One 2016;11:e0164269. [CrossRef]
  • 30. Sueblinvong V, Weiss DJ. Cell therapy approaches for lung diseases: current status. Curr Opin Pharmacol 2009;9:268-73. [CrossRef]
  • 31. Iyer SS, Co C, Rojas M. Mesenchymal stem cells and inflammatory lung diseases. Panminerva Med 2009;51:5-16.
  • 32. Weiss DJ, Casaburi R, Flannery R, et al. A Placebo-Controlled Randomized Trial of Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease. Chest 2013;143:1590-8. [CrossRef]
  • 33. Ribeiro-Paes JT, Bilaqui A, Greco OT, et al. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis 2011;6:63-71.[CrossRef]
  • 34. Ingenito EP, Tsai L, Murthy S, et al. Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant 2012;21:175-89. [CrossRef]
  • 35. de Oliveira HG, Cruz FF, Antunes MA, et al. Combined Bone Marrow-Derived Mesenchymal Stromal Cell Therapy and OneWay Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial. Stem Cells Transl Med 2017;6:962-9. [CrossRef]
  • 36. Ohnishi K, Takagi M, Kurokawa Y, et al. Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest 1998;78:1077-87.
  • 37. Russell RE, Culpitt SV, DeMatos C, et al. Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2002;26:602-9. [CrossRef]
  • 38. Finlay GA, O'Driscoll LR, Russell KJ, et al. Matrix metalloproteinase expression and production by alveolar macrophages in emphysema. Am J Respir Crit Care Med 1997;156:240-7. [CrossRef]
  • 39. Atkinson JJ, Lutey BA, Suzuki Y, et al. The role of matrix metalloproteinase-9 in cigarette smoke-induced emphysema. Am J Respir Crit Care Med 2011;183:876-84. [CrossRef]
  • 40. D'Armiento JM, Goldklang MP, Hardigan AA, et al. Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. PLoS One 2013;8:e56352. [CrossRef]
  • 41. Jung K, Lein M, Laube C, et al. Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood. Clin Chim Acta 2001;314:241-4. [CrossRef]
  • 42. Jung K, Lein M, Roemer A, et al. Circulating gelatinase B (MMP9)--the impact of the preanalytical step of blood collection. Matrix Biol 2002;21:381-2. [CrossRef]
  • 43. Ishikawa T, Aoshiba K, Yokohori N, et al. Macrophage colonystimulating factor aggravates rather than regenerates emphysematous lungs in mice. Respiration 2006;73:538-45. [CrossRef]
  • 44. Schols AM, Slangen J, Volovics L, et al. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1791-7. [CrossRef]
  • 45. Bolton CE, Ionescu AA, Shiels KM, et al. Associated loss of fatfree mass and bone mineral density in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:1286-93. [CrossRef]
  • 46. Keatings VM, Collins PD, Scott DM, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530-4. [CrossRef]
  • 47. Eid AA, Ionescu AA, Nixon LS, et al. Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:1414-8. [CrossRef]
  • 48. Di Francia M, Barbier D, Mege JL, et al. Tumor necrosis factoralpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;150:1453-5. [CrossRef]
  • 49. Takabatake N, Nakamura H, Abe S, et al. The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1179-84. [CrossRef]
  • 50. Langen RC, Schols AM, Kelders MC, et al. Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation. Am J Respir Cell Mol Biol 2006;35:689- 96. [CrossRef]
  • 51. Lewis MI, Zhan WZ, Sieck GC. Adaptations of the diaphragm in emphysema. J Appl Physiol 1992;72:934-43. [CrossRef]
  • 52. Marchand E, De Leyn P, Gayan-Ramirez G, et al. Lung volume reduction surgery does not improve diaphragmatic contractile properties or atrophy in hamsters with elastase-induced emphysema. Am J Respir Crit Care Med 2000;162:1052-7. [CrossRef]
  • 53. Degens H, Swisher AK, Heijdra YF, et al. Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster. Am J Physiol Regul Integr Comp Physiol 2007;293:R135-44.[CrossRef]
APA Yildiz Gulhan P, ekici m, Ekici A, Niyaz M, Gülhan M, Ercin M, aksoy n (2020). Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. , 14 - 20. 10.5152/TurkThoracJ.2019.180136
Chicago Yildiz Gulhan Pinar,ekici mehmet,Ekici Aydanur,Niyaz Mehmet,Gülhan Muhammet,Ercin Mustafa Emre,aksoy nurkan Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. (2020): 14 - 20. 10.5152/TurkThoracJ.2019.180136
MLA Yildiz Gulhan Pinar,ekici mehmet,Ekici Aydanur,Niyaz Mehmet,Gülhan Muhammet,Ercin Mustafa Emre,aksoy nurkan Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. , 2020, ss.14 - 20. 10.5152/TurkThoracJ.2019.180136
AMA Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. . 2020; 14 - 20. 10.5152/TurkThoracJ.2019.180136
Vancouver Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. . 2020; 14 - 20. 10.5152/TurkThoracJ.2019.180136
IEEE Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n "Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats." , ss.14 - 20, 2020. 10.5152/TurkThoracJ.2019.180136
ISNAD Yildiz Gulhan, Pinar vd. "Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats". (2020), 14-20. https://doi.org/10.5152/TurkThoracJ.2019.180136
APA Yildiz Gulhan P, ekici m, Ekici A, Niyaz M, Gülhan M, Ercin M, aksoy n (2020). Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. Turkish Thoracic Journal, 21(1), 14 - 20. 10.5152/TurkThoracJ.2019.180136
Chicago Yildiz Gulhan Pinar,ekici mehmet,Ekici Aydanur,Niyaz Mehmet,Gülhan Muhammet,Ercin Mustafa Emre,aksoy nurkan Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. Turkish Thoracic Journal 21, no.1 (2020): 14 - 20. 10.5152/TurkThoracJ.2019.180136
MLA Yildiz Gulhan Pinar,ekici mehmet,Ekici Aydanur,Niyaz Mehmet,Gülhan Muhammet,Ercin Mustafa Emre,aksoy nurkan Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. Turkish Thoracic Journal, vol.21, no.1, 2020, ss.14 - 20. 10.5152/TurkThoracJ.2019.180136
AMA Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. Turkish Thoracic Journal. 2020; 21(1): 14 - 20. 10.5152/TurkThoracJ.2019.180136
Vancouver Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats. Turkish Thoracic Journal. 2020; 21(1): 14 - 20. 10.5152/TurkThoracJ.2019.180136
IEEE Yildiz Gulhan P,ekici m,Ekici A,Niyaz M,Gülhan M,Ercin M,aksoy n "Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats." Turkish Thoracic Journal, 21, ss.14 - 20, 2020. 10.5152/TurkThoracJ.2019.180136
ISNAD Yildiz Gulhan, Pinar vd. "Therapeutic Treatment with Abdominal Adipose Mesenchymal Cells Does Not Prevent Elastase-Induced Emphysema in Rats". Turkish Thoracic Journal 21/1 (2020), 14-20. https://doi.org/10.5152/TurkThoracJ.2019.180136