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Stem Cells International
Volume 2017, Article ID 5237063, 12 pages
https://doi.org/10.1155/2017/5237063
Clinical Study

Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic Heart Disease (MyStromalCell Trial): A Randomized Placebo-Controlled Study

1Department of Cardiology & Cardiac Catheterization Laboratory 2014, The Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
2Department of Plastic Surgery, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
3Department of Radiology, Diagnostic Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
4Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
5Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark

Correspondence should be addressed to Abbas Ali Qayyum; kd.hnoiger@muyyaQ.ilA.sabbA

Received 23 June 2017; Revised 21 September 2017; Accepted 12 October 2017; Published 3 December 2017

Academic Editor: Wojtek Wojakowski

Copyright © 2017 Abbas Ali Qayyum et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Finegold, P. Asaria, and D. P. Francis, “Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations,” International Journal of Cardiology, vol. 168, no. 2, pp. 934–945, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. A. E. Moran, M. H. Forouzanfar, G. A. Roth et al., “The global burden of ischemic heart disease in 1990 and 2010: the global burden of disease 2010 study,” Circulation, vol. 129, no. 14, pp. 1493–1501, 2014. View at Publisher · View at Google Scholar · View at Scopus
  3. B. M. Strem, K. C. Hicok, M. Zhu et al., “Multipotential differentiation of adipose tissue-derived stem cells,” The Keio Journal of Medicine, vol. 54, no. 3, pp. 132–141, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. I. Bochev, G. Elmadjian, D. Kyurkchiev et al., “Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro,” Cell Biology International, vol. 32, no. 4, pp. 384–393, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. J. K. Fraser, R. Schreiber, B. Strem et al., “Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes,” Nature Clinical Practice Cardiovascular Medicine, vol. 3, pp. S33–S37, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Heydarkhan-Hagvall, K. Schenke-Layland, J. Q. Yang et al., “Human adipose stem cells: a potential cell source for cardiovascular tissue engineering,” Cells, Tissues, Organs, vol. 187, no. 4, pp. 263–274, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. M. N. Helder, M. Knippenberg, J. Klein-Nulend, and P. I. J. M. Wuisman, “Stem cells from adipose tissue allow challenging new concepts for regenerative medicine,” Tissue Engineering, vol. 13, no. 8, pp. 1799–1808, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. T. D. Henry, C. J. Pepine, C. R. Lambert et al., “The Athena trials: autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction,” Catheterization and Cardiovascular Interventions, vol. 89, no. 2, pp. 169–177, 2017. View at Publisher · View at Google Scholar · View at Scopus
  9. E. C. Perin, R. Sanz-Ruiz, P. L. Sanchez et al., “Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: the PRECISE trial,” American Heart Journal, vol. 168, no. 1, pp. 88–95.e2, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Friis, M. Haack-Sorensen, A. B. Mathiasen et al., “Mesenchymal stromal cell derived endothelial progenitor treatment in patients with refractory angina,” Scandinavian Cardiovascular Journal, vol. 45, no. 3, pp. 161–168, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. J. M. Hare, J. E. Fishman, G. Gerstenblith et al., “Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial,” JAMA, vol. 308, no. 22, pp. 2369–2379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. A. B. Mathiasen, M. Haack-Sorensen, E. Jorgensen, and J. Kastrup, “Autotransplantation of mesenchymal stromal cells from bone-marrow to heart in patients with severe stable coronary artery disease and refractory angina - final 3-year follow-up,” International Journal of Cardiology, vol. 170, no. 2, pp. 246–251, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. A. B. Mathiasen, A. A. Qayyum, E. Jorgensen et al., “Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial),” European Heart Journal, vol. 36, no. 27, pp. 1744–1753, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Kim, H. Kim, H. Cho, Y. Bae, K. Suh, and J. Jung, “Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia,” Cellular Physiology and Biochemistry, vol. 20, no. 6, pp. 867–876, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. A. J. Poncelet, A. L. Hiel, J. Vercruysse, D. Hermans, F. Zech, and P. Gianello, “Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model,” European Journal of Cardio-Thoracic Surgery, vol. 38, no. 6, pp. 781–787, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Str ioga, S. Viswanathan, A. Darinskas, O. Slaby, and J. Michalek, “Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells,” Stem Cells and Development, vol. 21, no. 14, pp. 2724–2752, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Oswald, S. Boxberger, B. Jorgensen et al., “Mesenchymal stem cells can be differentiated into endothelial cells in vitro,” Stem Cells, vol. 22, no. 3, pp. 377–384, 2004. View at Publisher · View at Google Scholar
  18. B. Follin, J. Tratwal, M. Haack-Sorensen, J. J. Elberg, J. Kastrup, and A. Ekblond, “Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease,” Journal of Translational Medicine, vol. 11, no. 1, p. 219, 2013. View at Publisher · View at Google Scholar · View at Scopus
  19. J. H. Houtgraaf, W. K. den Dekker, B. M. van Dalen et al., “First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction,” Journal of the American College of Cardiology, vol. 59, no. 5, pp. 539-540, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. A. A. Qayyum, M. Haack-Sorensen, A. B. Mathiasen, E. Jørgensen, A. Ekblond, and J. Kastrup, “Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design,” Regenerative Medicine, vol. 7, no. 3, pp. 421–428, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. A. A. Qayyum, J. T. Kuhl, A. Kjaer, P. Hasbak, K. F. Kofoed, and J. Kastrup, “Semi-quantitative myocardial perfusion measured by computed tomography in patients with refractory angina: a head-to-head comparison with quantitative rubidium-82 positron emission tomography as reference,” Clinical Physiology and Functional Imaging, vol. 37, no. 5, pp. 481–488, 2015. View at Publisher · View at Google Scholar
  22. A. A. Qayyum, J. T. Kuhl, A. B. Mathiasen et al., “Value of cardiac 320-multidetector computed tomography and cardiac magnetic resonance imaging for assessment of myocardial perfusion defects in patients with known chronic ischemic heart disease,” The International Journal of Cardiovascular Imaging, vol. 29, no. 7, pp. 1585–1593, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. E. Briones, J. R. Lacalle, I. Marin-Leon, and J. R. Rueda, “Transmyocardial laser revascularization versus medical therapy for refractory angina,” Cochrane Database of Systematic Reviews, no. 2, article CD003712, 2015. View at Google Scholar
  24. D. W. Losordo, R. A. Schatz, C. J. White et al., “Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial,” Circulation, vol. 115, no. 25, pp. 3165–3172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. T. J. Povsic, T. D. Henry, J. H. Traverse et al., “The RENEW trial: efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina,” JACC: Cardiovascular Interventions, vol. 9, no. 15, pp. 1576–1585, 2016. View at Publisher · View at Google Scholar · View at Scopus
  26. D. W. Losordo, T. D. Henry, C. Davidson et al., “Intramyocardial, autologous CD34+ cell therapy for refractory angina,” Circulation Research, vol. 109, no. 4, pp. 428–436, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Mazo, V. Planat-Benard, G. Abizanda et al., “Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction,” European Journal of Heart Failure, vol. 10, no. 5, pp. 454–462, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Wang, J. Deng, W. Tian et al., “Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: an MR imaging study of rat hearts,” American Journal of Physiology Heart and Circulatory Physiology, vol. 297, no. 3, pp. H1020–H1031, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. X. Bai and E. Alt, “Myocardial regeneration potential of adipose tissue-derived stem cells,” Biochemical and Biophysical Research Communications, vol. 401, no. 3, pp. 321–326, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. March 2016, http://ir.cytori.com/investor-relations/News/news-details/2013/Cytori-Reports-First-Half-and-2nd-Quarter-2013-Business-and-Financial-Results/default.aspx.
  31. R. J. van, J. J. Bax, S. L. Beeres et al., “Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial,” JAMA, vol. 301, no. 19, pp. 1997–2004, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. E. Diderholm, B. Andrén, G. Frostfeldt et al., “Effects of an early invasive strategy on ischemia and exercise tolerance among patients with unstable coronary artery disease,” The American Journal of Medicine, vol. 115, no. 8, pp. 606–612, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Haack-Sorensen, B. Follin, M. Juhl et al., “Culture expansion of adipose derived stromal cells. A closed automated quantum cell expansion system compared with manual flask-based culture,” Journal of Translational Medicine, vol. 14, no. 1, p. 319, 2016. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Tongers, D. W. Losordo, and U. Landmesser, “Stem and progenitor cell-based therapy in ischaemic heart disease: promise, uncertainties, and challenges,” European Heart Journal, vol. 32, no. 10, pp. 1197–1206, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. T. J. Povsic, C. Junge, A. Nada et al., “A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study,” American Heart Journal, vol. 165, no. 6, pp. 854–861.e2, 2013. View at Publisher · View at Google Scholar · View at Scopus