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Cell therapy in myocardial infarction: emphasis on the role of MRI

  • Cardiac
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An Erratum to this article was published on 21 February 2008

Abstract

Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points.

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References

  1. Braunwald E (1989) Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded? Circulation 79:441–444

    PubMed  CAS  Google Scholar 

  2. Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 35:569–582

    PubMed  CAS  Google Scholar 

  3. Steg PG, Lopez-Sendon J, Lopez de Sa E, Goodman SG, Gore JM, Anderson FA Jr, Himbert D, Allegrone J, Van de Werf F (2007) External validity of clinical trials in acute myocardial infarction. Arch Intern Med 167:68–73

    PubMed  Google Scholar 

  4. Bartunek J, Dimmeler S, Drexler H, Fernandez-Aviles F, Galinanes M, Janssens S, Martin J, Mathur A, Menasche P, Priori S (2006) The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart. Eur Heart J 27:1338–1340

    PubMed  Google Scholar 

  5. Murry CE, Reinecke H, Pabon LM (2006) Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol 47:1777–1785

    PubMed  Google Scholar 

  6. Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856

    PubMed  CAS  Google Scholar 

  7. Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 85:1373–1416

    PubMed  CAS  Google Scholar 

  8. Marthur A, Martin JF (2004) Stem cells and repair of the heart. Lancet 364:183–192

    Google Scholar 

  9. Dimmeler S, Zeiher AM, Schneider MD (2005) Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 115:572–583

    PubMed  CAS  Google Scholar 

  10. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15

    PubMed  Google Scholar 

  11. Minami E, Laflamme MA, Saffitz JE, Murry CE (2005) Extracardiac progenitor cells repopulate most major cell types in the transplanted human heart. Circulation 112:2951–2958

    PubMed  Google Scholar 

  12. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    PubMed  CAS  Google Scholar 

  13. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7:430–436

    PubMed  CAS  Google Scholar 

  14. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Dimmeler S, Zeiher AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106:3009–3017

    PubMed  Google Scholar 

  15. Strauer BE, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C, Sorg RV, Kogler G, Wernet P, Muller HW, Köstering M (2005) Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol 46:1651–1658

    PubMed  Google Scholar 

  16. Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918

    PubMed  Google Scholar 

  17. Assmus B, Walter DH, Lehmann R, Honold J, Martin H, Dimmeler S, Zeiher AM, Schachinger V (2006) Intracoronary infusion of progenitor cells is not associated with aggravated restenosis development or atherosclerotic disease progression in patients with acute myocardial infarction. Eur Heart J 27:2989–2995

    PubMed  Google Scholar 

  18. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, De Bondt P, Van Haute I, Lootens N, Heyndrickx G, Wijns W (2005) Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation 112:I178–I183

    PubMed  Google Scholar 

  19. Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Schachinger V, Dimmeler S, Zeiher AM (2003) Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 108:2212–2218

    PubMed  CAS  Google Scholar 

  20. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H (2004) Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141–148

    PubMed  Google Scholar 

  21. Engelmann MG, Theiss HD, Hennig-Theiss C, Huber A, Wintersperger BJ, Werle-Ruedinger AE, Schoenberg SO, Steinbeck G, Franz WM (2006) Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial. J Am Coll Cardiol 48:1712–1721

    PubMed  CAS  Google Scholar 

  22. Zohnhöfer D, Ott I, Mehilli J, Schömig K, Michalk F, Ibrahim T, Meisetschläger G, von Wedel J, Bollwein H, Seyfarth M, Dirschinger J, Schmitt C, Schwaiger M, Kastrati A, Schömig A, for the REVIVAL-2 investigators (2006) Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. JAMA 295:1003–1010

    Google Scholar 

  23. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Müller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K (2006) Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 355:1199–1209

    PubMed  CAS  Google Scholar 

  24. Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, Kalantzi M, Herbots L, Sinnaeve P, Dens J, Maertens J, Rademakers F, Dymarkowski S, Gheysens O, Van Cleemput J, Bormans G, Nuyts J, Belmans A, Mortelmans L, Boogaerts M, Van de Werf F (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367:113–121

    PubMed  Google Scholar 

  25. Kang H-J, Lee H-Y, Na S-H, Chang S-A, Park K-W, Kim H-K, Kim S-Y, Chang H-J, Lee W, Kang WJ, Koo B-K, Kim Y-J, Lee DS, Sohn D-W, Han K-S, Oh B-H, Park Y- B, Kim H-S (2006) Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction. The MAGIC Cell-3-DES randomized, controlled trial. Circulation 114:I-145–I-151

    Google Scholar 

  26. Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Süselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher, for the REPAIR-AMI investigators (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221

    PubMed  Google Scholar 

  27. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 44:1690–1699

    PubMed  Google Scholar 

  28. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Dimmeler S, Zeiher AM (2006) Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 27:2775–2783

    PubMed  Google Scholar 

  29. Ripa RS, Jorgensen E, Wang Y, Thune JJ, Nilsson JC, Sondergaard L, Johnsen HE, Kober L, Grande P, Kastrup J (2006) Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST- elevation myocardial infarction. Result of the double-blind, randomized, placebo- controlled stem cells in myocardial infarction (STEMMI) trial. Circulation 113:1983–1992

    PubMed  CAS  Google Scholar 

  30. Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, Hecker H, Schaefer A, Arsenieve L, Hertenstein B, Ganser A, Drexler H (2006) Intracoronary bone marrow cell transfer after myocardial infarction. Eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST- elevation infarct regeneration) trial. Circulation 113:1287–1294

    PubMed  Google Scholar 

  31. Numaguchi Y, Sone T, Okumura K, Ishii M, Morita Y, Kubota R, Yokouchi K, Imai H, Harada M, Osanai H, Kondo T, Murohara (2006) The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 114:I114–I119

    PubMed  Google Scholar 

  32. Rosenzweig A (2006) Cardiac cell therapy—mixed results from mixed cells. N Engl J Med 355:1274–1277

    PubMed  CAS  Google Scholar 

  33. Hendrickx M, Hensen K, Clijsters C, Jongen H, Konickx R, Bijnens E, Ingels M, Jacobs A, Geukens R, Dendale P, Vijgen J, Dilling D, Steels P, Mees U, Rummens JL (2006) Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation. Results from a randomized controlled clinical trial. Circulation 114:I101–I107

    Google Scholar 

  34. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, Emmrich F, Kluge R, Kendziorra K, Sabri O, Schuler G, Hambrecht R (2005) Transplantation of blood- derived progenitor cells after recanalization of chronic coronary artery occlusion. First randomized and placebo-controlled study. Circ Res 97:756–762

    PubMed  CAS  Google Scholar 

  35. Forrester JS, Shah PK, Makkar RR (2006) Myocardial regeneration by stem cells: seeing the unseeable. J Am Coll Cardiol 48:1722–1724

    PubMed  Google Scholar 

  36. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190

    PubMed  CAS  Google Scholar 

  37. Fuster V, Sanz J, Viles-Gonzalez JF, Rajagopalan S (2006) The utility of magnetic resonance imaging in cardiac tissue regeneration trials. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S2–S7

    PubMed  Google Scholar 

  38. Rogers WJ, Meyer CH, Kramer CM (2006) Technology insight: in vivo cell tracking by use of MRI. Nat Clin Pract Cardiovasc Med 3:554–562

    PubMed  CAS  Google Scholar 

  39. Zhou R, Acton PD, Ferrari VA (2006) Imaging stem cells implanted in infarcted myocardium. J Am Coll Cardiol 48:2094–2106

    PubMed  Google Scholar 

  40. Jacobs RE, Fraser SE (1994) Magnetic resonance microscopy of embryonic cell lineages and movements. Science 263:681–684

    PubMed  CAS  Google Scholar 

  41. Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ, Price J, Hodges H (2002) Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage 17:803–811

    PubMed  Google Scholar 

  42. Modo M, Mellodew K, Cash D, Fraser SE, Meade TJ, Price J, Williams SC (2004) Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 21:311–317

    Google Scholar 

  43. Aime S, Barge A, Cabella C, Crich SG, Gianolio E (2004) Targeting cells with MR imaging probes based on paramagnetic Gd(III) chelates. Curr Pharm Biotechnol 5:509–518

    PubMed  CAS  Google Scholar 

  44. Daldrup-Link HE, Rudelius M, Metz S, Piontek G, Pichler B, Settles M, Heinzmann U, Schlegel J, Oostendorp RA, Rummeny EJ (2004) Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy. Eur J Nucl Med Mol Imaging 31:1312–1321

    PubMed  Google Scholar 

  45. Aoki I, Takahashi Y, Chuang KH, Silva AC, Igarashi T, Tanaka C, Childs RW, Koretsky AP (2006) Cell labeling for magnetic resonance imaging with the T1 agent manganese chloride. NMR Biomed 19:50–59

    PubMed  CAS  Google Scholar 

  46. Ahrens ET, Flores R, Xu H, Morel P (2005) In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 23:983–987

    PubMed  CAS  Google Scholar 

  47. Tannous BA, Grimm J, Perry KF, Chen JW, Weissleder R, Breakefield XO (2006) Metabolic biotinylation of cell surface receptors for in vivo imaging. Nat Methods 3:391–396

    PubMed  CAS  Google Scholar 

  48. Cohen B, Dafni H, Meir G, Harmelin A, Neeman M (2005) Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 7:109–117

    PubMed  CAS  Google Scholar 

  49. Genove G, DeMarco U, Xu H, Goins WF, Ahrens ET (2005) A new transgene reporter for in vivo magnetic resonance imaging. Nat Med 11:450–454

    PubMed  CAS  Google Scholar 

  50. Gilad AA, McMahon MT, Walczak P, Winnard PT Jr, Raman V, van Laarhoven HW, Skoglund CM, Bulte JW, van Zijl PC (2007) Artificial reporter gene providing MRI contrast based on proton exchange. Nat Biotechnol 25:217–219

    PubMed  CAS  Google Scholar 

  51. Corot C, Robert P, Idee JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504

    PubMed  CAS  Google Scholar 

  52. Stuckey DJ, Carr CA, Martin-Rendon E, Tyler DJ, Willmott C, Cassidy PJ, Hale SJ, Schneider JE, Tatton L, Harding SE (2006) Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart. Stem Cells 24:1968–1975

    PubMed  CAS  Google Scholar 

  53. Taupitz M, Wagner S, Schnorr J, Kravec I, Pilgrimm H, Bergmann-Fritsch H, Hamm B (2004) Phase I clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging. Invest Radiol 39:394–405

    PubMed  CAS  Google Scholar 

  54. McLachlan SJ, Morris MR, Lucas MA, Fisco RA, Eakins MN, Fowler DR, Scheetz RB, Olukotun AY (1994) Phase I clinical evaluation of a new iron oxide MR contrast agent. J Magn Reson Imaging 4:301–307

    PubMed  CAS  Google Scholar 

  55. Li W, Tutton S, Vu AT, Pierchala L, Li BS, Lewis JM, Prasad PV, Edelman RR (2005) First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Reson Imaging 21:46–52

    PubMed  Google Scholar 

  56. Clement O, Siauve N, Cuenod CA, Frija G (1998) Liver imaging with ferumoxides (Feridex): fundamentals, controversies, and practical aspects. Top Magn Reson Imaging 9:167–182

    PubMed  CAS  Google Scholar 

  57. Reimer P, Marx C, Rummeny EJ, Muller M, Lentschig M, Balzer T, Dietl KH, Sulkowski U, Berns T, Shamsi K (1997) SPIO-enhanced 2D-TOF MR angiography of the portal venous system: results of an intraindividual comparison. J Magn Reson Imaging 7:945–949

    PubMed  CAS  Google Scholar 

  58. Shapiro EM, Skrtic S, Koretsky AP (2005) Sizing it up: cellular MRI using micron-sized iron oxide particles. Magn Reson Med 53:329–338

    PubMed  Google Scholar 

  59. Reimer P, Tombach B (1998) Hepatic MRI with SPIO: detection and characterization of focal liver lesions. Eur Radiol 8:1198–1204

    PubMed  CAS  Google Scholar 

  60. Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499

    PubMed  Google Scholar 

  61. Dardzinski BJ, Schmithorst VJ, Holland SK, Boivin GP, Imagawa T, Watanabe S, Lewis JM, Hirsch R (2001) MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles. Magn Reson Imaging 19:1209–1216

    PubMed  CAS  Google Scholar 

  62. Turetschek K, Roberts TP, Floyd E, Preda A, Novikov V, Shames DM, Carter WO, Brasch RC (2001) Tumor microvascular characterization using ultrasmall superparamagnetic iron oxide particles (USPIO) in an experimental breast cancer model. J Magn Reson Imaging 13:882–888

    PubMed  CAS  Google Scholar 

  63. Berry I, Benderbous S, Ranjeva JP, Gracia-Meavilla D, Manelfe C, Le Bihan D (1996) Contribution of Sinerem used as blood-pool contrast agent: detection of cerebral blood volume changes during apnea in the rabbit. Magn Reson Med 36:415–419

    PubMed  CAS  Google Scholar 

  64. Metz S, Bonaterra G, Rudelius M, Settles M, Rummeny EJ, Daldrup-Link HE (2004) Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol 14:1851–1858

    PubMed  Google Scholar 

  65. Fleige G, Seeberger F, Laux D, Kresse M, Taupitz M, Pilgrimm H, Zimmer C (2002) In vitro characterization of two different ultrasmall iron oxide particles for magnetic resonance cell tracking. Invest Radiol 37:482–488

    PubMed  CAS  Google Scholar 

  66. Frank JA, Anderson SA, Kalsih H, Jordan EK, Lewis BK, Yocum GT, Arbab AS (2004) Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging. Cytotherapy 6:621–625

    Article  PubMed  CAS  Google Scholar 

  67. Bulte JW, Douglas T, Witwer B, Zhang SC, Strable E, Lewis BK, Zywicke H, Miller B, van Gelderen P, Moskowitz BM (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19:1141–1147

    PubMed  CAS  Google Scholar 

  68. Frank JA, Zywicke H, Jordan EK, Mitchell J, Lewis BK, Miller B, Bryant LH Jr, Bulte JW (2002) Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol 9(Suppl 2):S484–S487

    PubMed  Google Scholar 

  69. Arbab AS, Yocum GT, Kalish H, Jordan EK, Anderson SA, Khakoo AY, Read EJ, Frank JA (2004) Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood 104:1217–1223

    PubMed  CAS  Google Scholar 

  70. Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW (2004) Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 17:513–517

    PubMed  Google Scholar 

  71. Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, Frank JA (2005) Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 18:553–559

    PubMed  CAS  Google Scholar 

  72. Bulte JW, Kraitchman DL, Mackay AM, Pittenger MF (2004) Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 104:3410–3412; author reply 3412–3413

    PubMed  CAS  Google Scholar 

  73. Bulte JW, Ma LD, Magin RL, Kamman R, Hulstaert CE, Go KG, The TH, de Leij L (1993) Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles. Magn Reson Med 29:32–37

    PubMed  CAS  Google Scholar 

  74. Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA (1999) Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci USA 96:15256–15261

    PubMed  CAS  Google Scholar 

  75. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414

    PubMed  CAS  Google Scholar 

  76. Walczak P, Ruiz-Cabello J, Kedziorek DA, Gilad AA, Lin S, Barnett B, Qin L, Levitsky H, Bulte JW (2006) Magnetoelectroporation: improved labeling of neural stem cells and leukocytes for cellular magnetic resonance imaging using a single FDA-approved agent. Nanomedicine 2:89–94

    PubMed  CAS  Google Scholar 

  77. Walczak P, Kedziorek DA, Gilad AA, Lin S, Bulte JW (2005) Instant MR labeling of stem cells using magnetoelectroporation. Magn Reson Med 54:769–774

    PubMed  CAS  Google Scholar 

  78. Suzuki Y, Zhang S, Kundu P, Yeung AC, Robbins RC, Yang PC (2007) In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 57:1173–1179

    PubMed  CAS  Google Scholar 

  79. Bowen CV, Zhang X, Saab G, Gareau PJ, Rutt BK (2002) Application of the static dephasing regime theory to superparamagnetic iron-oxide loaded cells. Magn Reson Med 48:52–61

    PubMed  CAS  Google Scholar 

  80. Foster-Gareau P, Heyn C, Alejski A, Rutt BK (2003) Imaging single mammalian cells with a 1.5 T clinical MRI scanner. Magn Reson Med 49:968–971

    PubMed  Google Scholar 

  81. Mani V, Briley-Saebo KC, Itskovich VV, Samber DD, Fayad ZA (2006) Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T. Magn Reson Med 55:126–135

    PubMed  CAS  Google Scholar 

  82. Cunningham CH, Arai T, Yang PC, McConnell MV, Pauly JM, Conolly SM (2005) Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med 53:999–1005

    PubMed  CAS  Google Scholar 

  83. Stroh A, Faber C, Neuberger T, Lorenz P, Sieland K, Jakob PM, Webb A, Pilgrimm H, Schober R, Pohl EE (2005) In vivo detection limits of magnetically labeled embryonic stem cells in the rat brain using high-field (17.6 T) magnetic resonance imaging. Neuroimage 24:635–645

    PubMed  Google Scholar 

  84. Wu YL, Ye Q, Foley LM, Hitchens TK, Sato K, Williams JB, Ho C (2006) In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. Proc Natl Acad Sci USA 103:1852–1857

    PubMed  CAS  Google Scholar 

  85. Heyn C, Ronald JA, Ramadan SS, Snir JA, Barry AM, MacKenzie LT, Mikulis DJ, Palmieri D, Bronder JL, Steeg PS (2006) In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 56:1001–1010

    PubMed  Google Scholar 

  86. Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, Pessanha BS, Guttman MA, Varney TR, Martin BJ (2003) Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 108:1009–1014

    PubMed  Google Scholar 

  87. Baklanov DV, Demuinck ED, Thompson CA, Pearlman JD (2004) Novel double contrast MRI technique for intramyocardial detection of percutaneously transplanted autologous cells. Magn Reson Med 52:1438–1442

    PubMed  Google Scholar 

  88. Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P, Segars WP, Chen HH, Fritzges D, Izbudak I (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461

    PubMed  Google Scholar 

  89. Hombach V, Grebe O, Merkle N, Waldenmaier S, Hoher M, Kochs M, Wohrle J, Kestler HA (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26:549–557

    PubMed  Google Scholar 

  90. Bogaert J, Kalantzi M, Rademakers FE, Dymarkowski S, Janssens S (2007) Determinants and impact of microvascular obstruction in successfully reperfused ST-segment elevation myocardial infarction. Assessment by magnetic resonance imaging. Eur Radiol 17:2572–2580

    Google Scholar 

  91. Albert TS, Kim RJ, Judd RM (2006) Assessment of no-reflow regions using cardiac MRI. Basic Res Cardiol 101:383–390

    PubMed  Google Scholar 

  92. Tarantini G, Cacciavillani L, Corbetti F, Ramondo A, Marra MP, Bacchiega E, Napodano M, Bilato C, Razzolini R, Iliceto S (2005) Duration of ischemia is a major determinant of transmurality and severe microvascular obstruction after primary angioplasty: a study performed with contrast-enhanced magnetic resonance. J Am Coll Cardiol 46:1229–1235

    PubMed  Google Scholar 

  93. van den Bos EJ, Baks T, Moelker AD, Kerver W, van Geuns RJ, van der Giessen WJ, Duncker DJ, Wielopolski PA (2006) Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking? Eur Heart J 27:1620–1626

    PubMed  Google Scholar 

  94. Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, Hare JM, Bulte JW (2003) In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 107:2290–2293

    PubMed  Google Scholar 

  95. Kustermann E, Roell W, Breitbach M, Wecker S, Wiedermann D, Buehrle C, Welz A, Hescheler J, Fleischmann BK, Hoehn M (2005) Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation. NMR Biomed 18:362–370

    PubMed  Google Scholar 

  96. Tallheden T, Nannmark U, Lorentzon M, Rakotonirainy O, Soussi B, Waagstein F, Jeppsson A, Sjogren-Jansson E, Lindahl A, Omerovic E (2006) In vivo MR imaging of magnetically labeled human embryonic stem cells. Life Sci 79:999–1006

    PubMed  CAS  Google Scholar 

  97. Bulte JW (2005) Hot spot MRI emerges from the background. Nat Biotechnol 23:945–946

    PubMed  CAS  Google Scholar 

  98. Partlow KC, Chen J, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, Nolta JA, Caruthers SD, Lanza GM, Wickline SA (2007) 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. Faseb J 21:1647–1654

    PubMed  CAS  Google Scholar 

  99. McNab JA, Yung AC, Kozlowski P (2004) Tissue oxygen tension measurements in the Shionogi model of prostate cancer using 19F MRS and MRI. Magma 17:288–295

    PubMed  CAS  Google Scholar 

  100. Riess JG (2006) Perfluorocarbon-based oxygen delivery. Artif Cells Blood Substit Immobil Biotechnol 34:567–580

    PubMed  CAS  Google Scholar 

  101. Rickers C, Jerosch-Herold M, Hu X, Murthy N, Wang X, Kong H, Seethamraju RT, Weil J, Wilke NM (2003) Magnetic resonance image-guided transcatheter closure of atrial septal defects. Circulation 107:132–138

    PubMed  Google Scholar 

  102. Lederman RJ (2005) Cardiovascular interventional magnetic resonance imaging. Circulation 112:3009–3017

    PubMed  Google Scholar 

  103. Buecker A, Spuentrup E, Grabitz R, Freudenthal F, Muehler EG, Schaeffter T, van Vaals JJ, Gunther RW (2002) Magnetic resonance-guided placement of atrial septal closure device in animal model of patent foramen ovale. Circulation 106:511–515

    PubMed  Google Scholar 

  104. Spuentrup E, Ruebben A, Schaeffter T, Manning WJ, Gunther RW, Buecker A (2002) Magnetic resonance-guided coronary artery stent placement in a swine model. Circulation 105:874–879

    PubMed  Google Scholar 

  105. Razavi R, Hill DL, Keevil SF, Miquel ME, Muthurangu V, Hegde S, Rhode K, Barnett M, van Vaals J, Hawkes DJ (2003) Cardiac catheterisation guided by MRI in children and adults with congenital heart disease. Lancet 362:1877–1882

    PubMed  Google Scholar 

  106. Krueger JJ, Ewert P, Yilmaz S, Gelernter D, Peters B, Pietzner K, Bornstedt A, Schnackenburg B, Abdul-Khaliq H, Fleck E, Nagel E (2006) Magnetic resonance imaging-guided balloon angioplasty of coarctation of the aorta: a pilot study. Circulation 113:1093–1100

    PubMed  Google Scholar 

  107. Lederman RJ, Guttman MA, Peters DC, Thompson RB, Sorger JM, Dick AJ, Raman VK, McVeigh ER (2002) Catheter-based endomyocardial injection with real-time magnetic resonance imaging. Circulation 105:1282–1284

    PubMed  Google Scholar 

  108. Dick AJ, Guttman MA, Raman VK, Peters DC, Pessanha BS, Hill JM, Smith S, Scott G, McVeigh ER, Lederman RJ (2003) Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in Swine. Circulation 108:2899–2904

    PubMed  Google Scholar 

  109. Saeed M, Saloner D, Weber O, Martin A, Henk C, Higgins C (2005) MRI in guiding and assessing intramyocardial therapy. Eur Radiol 15:851–863

    PubMed  CAS  Google Scholar 

  110. Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Ann Intern Med 125:605–613

    PubMed  CAS  Google Scholar 

  111. Arnesen H, Lunde K, Aakhus S, Forfang K (2007) Cell therapy in myocardial infarction. Lancet 369:2142–2143

    PubMed  Google Scholar 

  112. Wu KC, Zerhouni EA, Judd RM, Lugo-Olivieri CH, Barouch LA, Schulman SP, Blumenthal RS, Lima JA (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97:765–772

    PubMed  CAS  Google Scholar 

  113. Gerber BL, Rochitte CE, Melin JA, McVeigh ER, Bluemke DA, Wu KC, Becker LC, Lima JA (2000) Microvascular obstruction and left ventricular remodeling early after acute myocardial infarction. Circulation 101:2734–2741

    PubMed  CAS  Google Scholar 

  114. Penn MS (2006) Stem-cell therapy after acute myocardial infarction: the focus should be on those at risk. Lancet 367:87–88

    PubMed  Google Scholar 

  115. Verberne HJ, Dibbets-Schneider P, Spijkerboer A, Stokkel M, van Eck-Smit BL, Sokole EB (2006) Multicenter intercomparison assessment of consistency of left ventricular function from a gated cardiac SPECT phantom. J Nucl Cardiol 13:801–810

    PubMed  Google Scholar 

  116. Vallejo E, Dione DP, Bruni WL, Constable RT, Borek PP, Soares JP, Carr JG, Condos SG, Wackers FJ, Sinusas AJ (2000) Reproducibility and accuracy of gated SPECT for determination of left ventricular volumes and ejection fraction: experimental validation using MRI. J Nucl Med 41:874–882; discussion 883–876

    PubMed  CAS  Google Scholar 

  117. Pattynama PM, Lamb HJ, van der Velde EA, van der Wall EE, de Roos A (1993) Left ventricular measurements with cine and spin-echo MR imaging: a study of reproducibility with variance component analysis. Radiology 187:261–268

    PubMed  CAS  Google Scholar 

  118. Moon JC, Lorenz CH, Francis JM, Smith GC, Pennell DJ (2002) Breath-hold FLASH and FISP cardiovascular MR imaging: left ventricular volume differences and reproducibility. Radiology 223:789–797

    PubMed  Google Scholar 

  119. Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJ, Cleland JG, Pennell DJ (2000) Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 21:1387–1396

    PubMed  CAS  Google Scholar 

  120. Marcus JT, Gotte MJ, DeWaal LK, Stam MR, Van der Geest RJ, Heethaar RM, Van Rossum AC (1999) The influence of through-plane motion on left ventricular volumes measured by magnetic resonance imaging: implications for image acquisition and analysis. J Cardiovasc Magn Reson 1:1–6

    PubMed  CAS  Google Scholar 

  121. Bogaert J (2005) Cardiac function. In: Bogaert J, Dymarkowski S, Taylor AM (ed) Clinical cardiac MRI. Springer, Berlin Heidelberg, pp 99–141

    Google Scholar 

  122. Bogaert J, Rademakers FE (2001) Regional nonuniformity of normal adult human left ventricle. Am J Physiol Heart Circ Physiol 280:H610–H620

    PubMed  CAS  Google Scholar 

  123. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105:539–542

    PubMed  Google Scholar 

  124. Zerhouni EA, Parish DM, Rogers WJ, Yang A, Shapiro EP (1988) Human heart: tagging with MR imaging-a method for noninvasive assessment of myocardial motion. Radiology 169:59–63

    PubMed  CAS  Google Scholar 

  125. Bogaert J, Maes A, Van de Werf F, Bosmans H, Herregods MC, Nuyts J, Desmet W, Mortelmans L, Marchal G, Rademakers FE (1999) Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function. Circulation 99:36–43

    PubMed  CAS  Google Scholar 

  126. Amado LC, Schuleri KH, Saliaris AP, Boyle AJ, Helm R, Oskouei B, Centola M, Eneboe V, Young R, Lima JA (2006) Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 48:2116–2124

    PubMed  Google Scholar 

  127. Zeng L, Hu Q, Wang X, Mansoor A, Lee J, Feygin J, Chang G, Suntharalingam P, Boozer S, Mhashilkar A, Panetta CJ, Swingen C, Deans R, From AHL, Bache RJ, Verfaillie CM, Zhang J (2007) Bioenergetic and functional consequences of bone marrow-derived multipotent progenitor cell transplantation in hearts with postinfarction left ventricular remodelling. Circulation 115:1866–1875

    PubMed  Google Scholar 

  128. Janssens S, Theunissen K, Boogaerts M, Van de Werf F (2006) Bone marrow cell transfer in acute myocardial infarction. Nat Clin Pract Cardiovasc Med 3(Suppl 1):S69–S72

    PubMed  Google Scholar 

  129. Bogaert J, Kalantzi M, Dymarkowski S, Janssens S (2006) Importance of intramyocardial hemorrhage in acute myocardial infarction: assessment with MRI. J. Cardiovasc Magn Reson 8:76–77

    Google Scholar 

  130. Simonetti OP, Kim RJ, Fieno DS, Hillenbrand HB, Wu E, Bundy JM, Finn JP, Judd RM (2001) An improved MR imaging technique for the visualization of myocardial infarction. Radiology 218:215–223

    PubMed  CAS  Google Scholar 

  131. Wagner A, Mahrholdt H, Holly TA, Elliott MD, Regenfus M, Parker M, Klocke FJ, Bonow RO, Kim RJ, Judd RM (2003) Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet 361:374–379

    PubMed  Google Scholar 

  132. Wagner A, Mahrholdt H, Thomson L, Hager S, Meinhardt G, Rehwald W, Parker M, Shah D, Sechtem U, Kim RJ, Judd RM (2006) Effects of time, dose, and inversion time for acute myocardial infarct size measurements based on magnetic resonance imaging-delayed contrast enhancement. J Am Coll Cardiol 47:2027–2033

    PubMed  Google Scholar 

  133. Mahrholdt H, Wagner A, Holly TA, Elliott MD, Bonow RO, Kim RJ, Judd RM (2002) Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging. Circulation 106:2322–2327

    PubMed  CAS  Google Scholar 

  134. Aletras AH, Tilak GS, Natanzon A, Hsu LY, Gonzalez FM, Hoyt RF Jr, Arai AE (2006) Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations. Circulation 113:1865–1870

    PubMed  Google Scholar 

  135. Ochiai K, Shimada T, Murakami Y, Ishibashi Y, Sano K, Kitamura J, Inoue S, Murakami R, Kawamitsu H, Sugimura K (1999) Hemorrhagic myocardial infarction after coronary reperfusion detected in vivo by magnetic resonance imaging in humans: prevalence and clinical implications. J Cardiovasc Magn Reson 1:247–256

    PubMed  CAS  Google Scholar 

  136. Amado LC, Gerber BL, Gupta SN, Rettmann DW, Szarf G, Schock R, Nasir K, Kraitchman DL, Lima JA (2004) Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol 44:2383–2389

    PubMed  Google Scholar 

  137. Jugdutt BI (2003) Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation 108:1395–1403

    PubMed  Google Scholar 

  138. Schuster MD, Kocher AA, Seki T, Martens TP, Xiang G, Homma S, Itescu S (2004) Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physiol Heart Circ Physiol 287:H525–H532

    PubMed  CAS  Google Scholar 

  139. Erbs S, Linke A, Schachinger V, Assmus B, Thiele H, Diederich KW, Hoffmann C, Dimmeler S, Tonn T, Hambrecht R, Zeiher AM, Schuler G (2007) Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction. The Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) Trial. Circulation 116:366–374

    Google Scholar 

  140. Christian TF, Rettmann DW, Aletras AH, Liao SL, Taylor JL, Balaban RS, Arai AE (2004) Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging. Radiology 232:677–684

    PubMed  Google Scholar 

  141. Hogemann D, Josephson L, Weissleder R, Basilion JP (2000) Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug Chem 11:941–946

    PubMed  CAS  Google Scholar 

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  1. Department of Radiology, University Hospital K.U.L., Herestraat 49, 3000, Leuven, Belgium

    Yuxiang Ye & Jan Bogaert

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00330-007-0806-8

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Ye, Y., Bogaert, J. Cell therapy in myocardial infarction: emphasis on the role of MRI. Eur Radiol 18, 548–569 (2008). https://doi.org/10.1007/s00330-007-0777-9

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