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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 354605, 10 pages
http://dx.doi.org/10.1155/2012/354605
Review Article

Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

1Molecular Cardiology Laboratory, Fondazione Cardiocentro Ticino, Via Tesserete, 6900 Lugano, Switzerland
2Ultrastructural Pathology, “Victor Babeş” National Institute of Pathology, 99-101 Spl. Independentei, 050096 Bucharest 5, Romania
3Department of Cardiology, Centre Hospitalier Universitaire Vaudois (CHUV), Avenue du Bugnon, 1011 Lausanne, Switzerland

Received 18 June 2012; Accepted 16 July 2012

Academic Editor: Ken-ichi Isobe

Copyright © 2012 Lucio Barile 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. D. Orlic, J. Kajstura, S. Chimenti et al., “Bone marrow cells regenerate infarcted myocardium,” Nature, vol. 410, no. 6829, pp. 701–705, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. L. B. Balsam, A. J. Wagers, J. L. Christensen, T. Kofidis, I. L. Weissmann, and R. C. Robbins, “Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium,” Nature, vol. 428, no. 6983, pp. 668–673, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. C. E. Murry, M. H. Soonpaa, H. Reinecke et al., “Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts,” Nature, vol. 428, no. 6983, pp. 664–668, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Stamm, B. Westphal, H. D. Kleine et al., “Autologous bone-marrow stem-cell transplantation for myocardial regeneration,” The Lancet, vol. 361, no. 9351, pp. 45–46, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. K. C. Wollert, G. P. Meyer, J. Lotz et al., “Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial,” The Lancet, vol. 364, no. 9429, pp. 141–148, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. V. Schächinger, S. Erbs, A. Elsässer et al., “Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction,” The New England Journal of Medicine, vol. 355, no. 12, pp. 1210–1221, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. B. Assmus, J. Honold, V. Schächinger et al., “Transcoronary transplantation of progenitor cells after myocardial infarction,” The New England Journal of Medicine, vol. 355, no. 12, pp. 1222–1232, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Janssens, C. Dubois, J. Bogaert et al., “Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial,” The Lancet, vol. 367, no. 9505, pp. 113–121, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Lunde, S. Solheim, S. Aakhus et al., “Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction,” The New England Journal of Medicine, vol. 355, no. 12, pp. 1199–1209, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. E. Forte, I. Chimenti, L. Barile et al., “Cardiac cell therapy: the next (re)generation,” Stem Cell Reviews and Reports, vol. 7, pp. 1018–1030, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Chavakis, M. Koyanagi, and S. Dimmeler, “Enhancing the outcome of cell therapy for cardiac repair: progress from bench to bedside and back,” Circulation, vol. 121, no. 2, pp. 325–335, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Abdel-Latif, R. Bolli, I. M. Tleyjeh et al., “Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis,” Archives of Internal Medicine, vol. 167, no. 10, pp. 989–997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. K. C. Wollert and H. Drexler, “Cell therapy for the treatment of coronary heart disease: a critical appraisal,” Nature Reviews Cardiology, vol. 7, no. 4, pp. 204–215, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. D. M. Leistner, U. Fischer-Rasokat, J. Honold et al., “Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy,” Clinical Research in Cardiology, vol. 100, no. 10, pp. 925–934, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Dimmeler and A. Leri, “Aging and disease as modifiers of efficacy of cell therapy,” Circulation Research, vol. 102, no. 11, pp. 1319–1330, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Ebelt, M. Jungblut, Y. Zhang et al., “Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines,” Stem Cells, vol. 25, no. 1, pp. 236–244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. K. R. Vrijsena, S. A. J. Chamuleaua, W. A. Noorta, P. A. Doevendansa, and J. P. G. Sluijtera, “Stem cell therapy for end-stage heart failure: indispensable role for the cell?” Current Opinion in Organ Transplantation, vol. 14, no. 5, pp. 560–565, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau, “Paracrine mechanisms in adult stem cell signaling and therapy,” Circulation Research, vol. 103, no. 11, pp. 1204–1219, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Ausoni and S. Sartore, “The cardiovascular unit as a dynamic player in disease and regeneration,” Trends in Molecular Medicine, vol. 15, no. 12, pp. 543–552, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Urbanek, D. Cesselli, M. Rota et al., “Stem cell niches in the adult mouse heart,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 24, pp. 9226–9231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. A. P. Beltrami, L. Barlucchi, D. Torella et al., “Adult cardiac stem cells are multipotent and support myocardial regeneration,” Cell, vol. 114, no. 6, pp. 763–776, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Oh, S. B. Bradfute, T. D. Gallardo et al., “Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 21, pp. 12313–12318, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. H. C. Ott, T. S. Matthiesen, J. Brechtken et al., “The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells,” Nature Clinical Practice Cardiovascular Medicine, vol. 4, supplement 1, pp. S27–S39, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Bearzi, M. Rota, T. Hosoda et al., “Human cardiac stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 35, pp. 14068–14073, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. R. R. Smith, L. Barile, H. C. Cho et al., “Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens,” Circulation, vol. 115, no. 7, pp. 896–908, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Linke, P. Müller, D. Nurzynska et al., “Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 25, pp. 8966–8971, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. A. M. Smits, P. van Vliet, C. H. Metz et al., “Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology,” Nature Protocols, vol. 4, no. 2, pp. 232–243, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Barile, I. Chimenti, R. Gaetani et al., “Cardiac stem cells: isolation, expansion and experimental use for myocardial regeneration,” Nature Clinical Practice Cardiovascular Medicine, vol. 4, supplement 1, pp. S9–S14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Barile, E. Messina, A. Giacomello, and E. Marbán, “Endogenous cardiac stem cells,” Progress in Cardiovascular Diseases, vol. 50, no. 1, pp. 31–48, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. G. M. Ellison, V. Galuppo, C. Vicinanza et al., “Cardiac stem and progenitor cell identification: different markers for the same cell?” Frontiers in Bioscience, vol. 2, pp. 641–652, 2010. View at Scopus
  31. L. Barile, F. Cerisoli, G. Frati et al., “Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart,” Journal of Cellular and Molecular Medicine, vol. 15, no. 1, pp. 63–71, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. S. S. Fazel, L. Chen, D. Angoulvant et al., “Activation of c-kit is necessary for mobilization of reparative bone marrow progenitor cells in response to cardiac injury,” The FASEB Journal, vol. 22, no. 3, pp. 930–940, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. L. W. van Laake, L. Qian, P. Cheng et al., “Reporter-based isolation of induced pluripotent stem cell-and embryonic stem cell-derived cardiac progenitors reveals limited gene expression variance,” Circulation Research, vol. 107, no. 3, pp. 340–347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Yoshida and S. Yamanaka, “IPS cells: a source of cardiac regeneration,” Journal of Molecular and Cellular Cardiology, vol. 50, no. 2, pp. 327–332, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. B. A. Reynolds and S. Weiss, “Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system,” Science, vol. 255, no. 5052, pp. 1707–1710, 1992. View at Scopus
  36. E. Pastrana, V. Silva-Vargas, and F. Doetsch, “Eyes wide open: a critical review of sphere-formation as an assay for stem cells,” Cell Stem Cell, vol. 8, no. 5, pp. 486–498, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. E. Messina, L. De Angelis, G. Frati et al., “Isolation and expansion of adult cardiac stem cells from human and murine heart,” Circulation Research, vol. 95, no. 9, pp. 911–921, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. T. S. Li, K. Cheng, S. T. Lee et al., “Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair,” Stem Cells, vol. 28, no. 11, pp. 2088–2098, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. D. R. Davis, Y. Zhang, R. R. Smith et al., “Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue,” PLoS ONE, vol. 4, no. 9, Article ID e7195, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. D. C. Andersen, P. Andersen, M. Schneider, H. B. Jensen, and S. P. Sheikh, “Murine “cardiospheres” are not a source of stem cells with cardiomyogenic potential,” Stem Cells, vol. 27, no. 7, pp. 1571–1581, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. I. Chimenti, R. R. Smith, T. S. Li et al., “Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice,” Circulation Research, vol. 106, no. 5, pp. 971–980, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Bolli, A. R. Chugh, D. D'Amario, et al., “Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial,” The Lancet, vol. 378, no. 9806, pp. 1847–1857, 2011.
  43. R. R. Makkar, R. R. Smith, K. Cheng, et al., “Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial,” The Lancet, vol. 379, no. 9819, pp. 895–904, 2012.
  44. X. L. Tang, G. Rokosh, S. K. Sanganalmath et al., “Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction,” Circulation, vol. 121, no. 2, pp. 293–305, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. A. M. Smits, L. W. Van Laake, K. Den Ouden et al., “Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium,” Cardiovascular Research, vol. 83, no. 3, pp. 527–535, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Kizana, E. Cingolani, and E. Marbán, “Non-cell-autonomous effects of vector-expressed regulatory RNAs in mammalian heart cells,” Gene Therapy, vol. 16, no. 9, pp. 1163–1168, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. P. R. Crisostomo, A. M. Abarbanell, M. Wang, T. Lahm, Y. Wang, and D. R. Meldrum, “Embryonic stem cells attenuate myocardial dysfunction and inflammation after surgical global ischemia via paracrine actions,” American Journal of Physiology, vol. 295, no. 4, pp. H1726–H1735, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Gnecchi, H. He, N. Noiseux et al., “Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement,” The FASEB Journal, vol. 20, no. 6, pp. 661–669, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Timmers, S. K. Lim, F. Arslan et al., “Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium,” Stem Cell Research, vol. 1, no. 2, pp. 129–137, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. F. Bönner, N. Borg, S. Burghoff, and J. Schrader, “Resident cardiac immune cells and expression of the ectonucleotidase enzymes CD39 and CD73 after ischemic injury,” PLoS One, vol. 7, Article ID e34730, 2012.
  51. S. F. Mause and C. Weber, “Microparticles: protagonists of a novel communication network for intercellular information exchange,” Circulation Research, vol. 107, no. 9, pp. 1047–1057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Théry, “Exosomes: secreted vesicles and intercellular communications,” F1000 Biology Reports, vol. 3, no. 1, article 15, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Théry, S. Amigorena, G. Raposo, and A. Clayton, “Isolation and characterization of exosomes from cell culture supernatants and biological fluids,” Current Protocols in Cell Biology, vol. 3, article 22, 2006. View at Scopus
  54. S. Mathivanan, H. Ji, and R. J. Simpson, “Exosomes: extracellular organelles important in intercellular communication,” Journal of Proteomics, vol. 73, no. 10, pp. 1907–1920, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. P. J. Quesenberry and J. M. Aliotta, “Cellular phenotype switching and microvesicles,” Advanced Drug Delivery Reviews, vol. 62, no. 12, pp. 1141–1148, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Mathivanan and R. J. Simpson, “ExoCarta: a compendium of exosomal proteins and RNA,” Proteomics, vol. 9, no. 21, pp. 4997–5000, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Ostrowski, N. B. Carmo, S. Krumeich et al., “Rab27a and Rab27b control different steps of the exosome secretion pathway,” Nature cell biology, vol. 12, no. 1, pp. 19–3013, 2010. View at Scopus
  58. H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee, and J. O. Lötvall, “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,” Nature Cell Biology, vol. 9, no. 6, pp. 654–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Ratajczak, K. Miekus, M. Kucia et al., “Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery,” Leukemia, vol. 20, no. 5, pp. 847–856, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Ohshima, K. Inoue, A. Fujiwara et al., “Let-7 microRNA family Is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line,” PLoS ONE, vol. 5, no. 10, Article ID e13247, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Montecalvo, A. T. Larregina, W. J. Shufesky, et al., “Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes,” Blood, vol. 119, no. 3, pp. 756–766, 2012.
  62. S. Sahoo, E. Klychko, T. Thorne, et al., “Exosomes from human CD34+ stem cells mediate their proangiogenic paracrine activity,” Circulation Research, vol. 109, pp. 724–728, 2011.
  63. K. R. Vrijsen, J. P. G. Sluijter, M. W. L. Schuchardt et al., “Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells,” Journal of Cellular and Molecular Medicine, vol. 14, no. 5, pp. 1064–1070, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. R. C. Lai, T. S. Chen, and S. K. Lim, “Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease,” Regenerative Medicine, vol. 6, no. 4, pp. 481–492, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. R. C. Lai, F. Arslan, M. M. Lee et al., “Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury,” Stem Cell Research, vol. 4, no. 3, pp. 214–222, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. E. Emmanouilidou, K. Melachroinou, T. Roumeliotis et al., “Cell-produced α-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival,” Journal of Neuroscience, vol. 30, no. 20, pp. 6838–6851, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. P. G. Sreekumar, R. Kannan, M. Kitamura et al., “αB crystallin is apically secreted within exosomes by polarized human retinal pigment epithelium and provides neuroprotection to adjacent cells,” PLoS ONE, vol. 5, no. 10, Article ID e12578, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Gherghiceanu and L. M. Popescu, “Cardiac telocytes—their junctions and functional implications,” Cell Tissue Research, vol. 348, no. 2, pp. 265–279, 2012.
  69. L. M. Popescu and M. S. Faussone-Pellegrini, “TELOCYTES—a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES,” Journal of Cellular and Molecular Medicine, vol. 14, no. 4, pp. 729–740, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Gherghiceanu and L. M. Popescu, “Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images,” Journal of Cellular and Molecular Medicine, vol. 14, no. 4, pp. 871–877, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. C. G. Manole, V. Cismaşiu, M. Gherghiceanu, and L. M. Popescu, “Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis,” Journal of Cellular and Molecular Medicine, vol. 15, no. 11, pp. 2284–2296, 2011. View at Publisher · View at Google Scholar
  72. H. Yagi, A. Soto-Gutierrez, B. Parekkadan et al., “Mesenchymal stem cells: mechanisms of immunomodulation and homing,” Cell Transplantation, vol. 19, no. 6-7, pp. 667–679, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. L. Zitvogel, A. Regnault, A. Lozier et al., “Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes,” Nature Medicine, vol. 4, no. 5, pp. 594–600, 1998. View at Publisher · View at Google Scholar · View at Scopus
  74. B. Escudier, T. Dorval, N. Chaput et al., “Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase 1 clinical trial,” Journal of Translational Medicine, vol. 3, article 10, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. M. A. Morse, J. Garst, T. Osada et al., “A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer,” Journal of Translational Medicine, vol. 3, article 9, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. S. Dai, D. Wei, Z. Wu et al., “Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer,” Molecular Therapy, vol. 16, no. 4, pp. 782–790, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. K. Malliaras, T. S. Li, D. Luthringer, et al., “Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells,” Circulation, vol. 125, pp. 100–112, 2012. View at Publisher · View at Google Scholar
  78. N. Chaput and C. Théry, “Exosomes: immune properties and potential clinical implementations,” Seminars in Immunopathology, vol. 33, no. 5, pp. 419–440, 2011. View at Publisher · View at Google Scholar · View at Scopus