Tuberculosis and Respiratory Diseases

  • 제78권3호
  • /
  • Pages.239-245
  • /
  • 2015
  • /
  • 1738-3536(pISSN)
  • /
  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
권호 표지
DOI QR코드

DOI QR Code

The Therapeutic Effects of Optimal Dose of Mesenchymal Stem Cells in a Murine Model of an Elastase Induced-Emphysema

  • Kim, You-Sun (Asan Institute for Life Sciences) ;
  • Kim, Ji-Young (Asan Institute for Life Sciences) ;
  • Huh, Jin Won (Departure of Pulmonary and Critical Care Medicine, Asan Medical Center) ;
  • Lee, Sei Won (Departure of Pulmonary and Critical Care Medicine, Asan Medical Center) ;
  • Choi, Soo Jin (Biomedical Research Institute, MEDIPOST Co. Ltd.) ;
  • Oh, Yeon-Mok (Asan Institute for Life Sciences)
  • 투고 : 2014.09.16
  • 심사 : 2014.12.05
  • 발행 : 2015.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

키워드

참고문헌

  1. Senior RM, Anthonisen NR. Chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med 1998;157(4 Pt 2):S139-47. https://doi.org/10.1164/ajrccm.157.4.nhlbi-12
  2. Sutherland ER, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med 2004;350:2689-97. https://doi.org/10.1056/NEJMra030415
  3. Churg A, Cosio M, Wright JL. Mechanisms of cigarette smokeinduced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 2008;294:L612-31. https://doi.org/10.1152/ajplung.00390.2007
  4. Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 2000;117:684-94. https://doi.org/10.1378/chest.117.3.684
  5. Yokohori N, Aoshiba K, Nagai A; Respiratory Failure Research Group in Japan. Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema. Chest 2004;125:626-32. https://doi.org/10.1378/chest.125.2.626
  6. Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146:545-55. https://doi.org/10.7326/0003-4819-146-8-200704170-00152
  7. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89. https://doi.org/10.1056/NEJMoa063070
  8. Huh JW, Kim SY, Lee JH, Lee JS, Van Ta Q, Kim M, et al. Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol 2011;301:L255-66. https://doi.org/10.1152/ajplung.00253.2010
  9. Longhini-Dos-Santos N, Barbosa-de-Oliveira VA, Kozma RH, Faria CA, Stessuk T, Frei F, et al. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema. Stem Cell Rev 2013;9:210-8. https://doi.org/10.1007/s12015-012-9419-y
  10. Schweitzer KS, Johnstone BH, Garrison J, Rush NI, Cooper S, Traktuev DO, et al. Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. Am J Respir Crit Care Med 2011;183:215-25. https://doi.org/10.1164/rccm.201001-0126OC
  11. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294-301. https://doi.org/10.1634/stemcells.2005-0342
  12. Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM. Adult bone marrow is a rich source of human mesenchymal ‘stem' cells but umbilical cord and mobilized adult blood are not. Br J Haematol 2003;121:368-74. https://doi.org/10.1046/j.1365-2141.2003.04284.x
  13. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med 2013;45:e54. https://doi.org/10.1038/emm.2013.94
  14. Saether EE, Chamberlain CS, Leiferman EM, Kondratko-Mittnacht JR, Li WJ, Brickson SL, et al. Enhanced medial collateral ligament healing using mesenchymal stem cells: dosage effects on cellular response and cytokine profile. Stem Cell Rev 2014;10:86-96. https://doi.org/10.1007/s12015-013-9479-7
  15. Richardson JD, Bertaso AG, Psaltis PJ, Frost L, Carbone A, Paton S, et al. Impact of timing and dose of mesenchymal stromal cell therapy in a preclinical model of acute myocardial infarction. J Card Fail 2013;19:342-53. https://doi.org/10.1016/j.cardfail.2013.03.011
  16. Cataldo D, Munaut C, Noel A, Frankenne F, Bartsch P, Foidart JM, et al. MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 2000;123:259-67. https://doi.org/10.1159/000024452
  17. Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, et al. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr 2014;164:966-72.e6. https://doi.org/10.1016/j.jpeds.2013.12.011
  18. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol 2009;54:2277-86. https://doi.org/10.1016/j.jacc.2009.06.055
  19. Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, et al. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 2010;69:1423-9. https://doi.org/10.1136/ard.2009.123463
  20. Haynesworth SE, Baber MA, Caplan AI. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro : effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996;166:585-92. https://doi.org/10.1002/(SICI)1097-4652(199603)166:3<585::AID-JCP13>3.0.CO;2-6
  21. Hegab AE, Kubo H, Yamaya M, Asada M, He M, Fujino N, et al. Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema. Mol Ther 2008;16:1417-26. https://doi.org/10.1038/mt.2008.137
  22. Katsha AM, Ohkouchi S, Xin H, Kanehira M, Sun R, Nukiwa T, et al. Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol Ther 2011;19:196-203. https://doi.org/10.1038/mt.2010.192
  23. Muyal JP, Muyal V, Kotnala S, Kumar D, Bhardwaj H. Therapeutic potential of growth factors in pulmonary emphysematous condition. Lung 2013;191:147-63. https://doi.org/10.1007/s00408-012-9438-0
  24. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 2000;106:1311-9. https://doi.org/10.1172/JCI10259
  25. Guan XJ, Song L, Han FF, Cui ZL, Chen X, Guo XJ, et al. Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors. J Cell Biochem 2013;114:323-35. https://doi.org/10.1002/jcb.24377
  26. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 2013;143:1590-8. https://doi.org/10.1378/chest.12-2094
  27. Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 2002;30:215-22. https://doi.org/10.1038/sj.bmt.1703650
  28. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999;5:309-13. https://doi.org/10.1038/6529

피인용 문헌

  1. Mesenchymal cells condensation-inducible mesh scaffolds for cartilage tissue engineering vol.85, pp.None, 2015, https://doi.org/10.1016/j.biomaterials.2016.01.048
  2. Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis vol.11, pp.6, 2015, https://doi.org/10.1371/journal.pone.0157099
  3. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials vol.23, pp.1, 2015, https://doi.org/10.1186/s12929-016-0289-5
  4. Lung Regeneration Therapy for Chronic Obstructive Pulmonary Disease vol.80, pp.1, 2017, https://doi.org/10.4046/trd.2017.80.1.1
  5. Can Youthful Mesenchymal Stem Cells from Wharton’s Jelly Bring a Breath of Fresh Air for COPD? vol.18, pp.11, 2015, https://doi.org/10.3390/ijms18112449
  6. Spleen Morphological Features Under Experimental Model of Multiple Organ Failure and Stem Cell Application vol.28, pp.1, 2015, https://doi.org/10.15407/cryo28.01.064
  7. Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease? vol.73, pp.6, 2015, https://doi.org/10.1136/thoraxjnl-2017-210672
  8. Cell-based Therapy for Chronic Obstructive Pulmonary Disease. Rebuilding the Lung vol.15, pp.suppl._4, 2015, https://doi.org/10.1513/annalsats.201808-534mg
  9. Potential Therapeutic Strategy in Chronic Obstructive Pulmonary Disease Using Pioglitazone-Augmented Wharton's Jelly-Derived Mesenchymal Stem Cells vol.82, pp.2, 2019, https://doi.org/10.4046/trd.2018.0044
  10. Identification of Putative Regulatory Alterations Leading to Changes in Gene Expression in Chronic Obstructive Pulmonary Disease vol.42, pp.4, 2019, https://doi.org/10.14348/molcells.2019.2442
  11. Functional and histologic effects after implanting pluripotent stem cells in a murine model with sphincterotomy vol.84, pp.2, 2019, https://doi.org/10.1016/j.rgmxen.2018.09.005
  12. Targeting Aging Pathways in Chronic Obstructive Pulmonary Disease vol.21, pp.18, 2020, https://doi.org/10.3390/ijms21186924
  13. Stem cell therapy for chronic obstructive pulmonary disease vol.134, pp.13, 2021, https://doi.org/10.1097/cm9.0000000000001596
  14. Mesenchymal stromal cells-based therapy in a murine model of elastase-induced emphysema: Simvastatin as a potential adjuvant in cellular homing vol.70, pp.None, 2015, https://doi.org/10.1016/j.pupt.2021.102075
  15. Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels vol.22, pp.1, 2021, https://doi.org/10.1186/s12931-021-01734-8