Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective

  • Peter J. Psaltis
  • Robert D. Simari
  • Martin Rodriguez-Porcel
Review Article

Abstract

Despite preclinical promise, the progress of cell-based therapy to clinical cardiovascular practice has been slowed by several challenges and uncertainties that have been highlighted by the conflicting results of human trials. Most telling has been the revelation that current strategies fall short of achieving sufficient retention and engraftment of cells to meet the ambitious objective of myocardial regeneration. This has sparked novel research into the refinement of cell biology and delivery to overcome these shortcomings. Within this context, molecular imaging has emerged as a valuable tool for providing noninvasive surveillance of cell fate in vivo. Direct and indirect labelling of cells can be coupled with clinically relevant imaging modalities, such as radionuclide single photon emission computed tomography and positron emission tomography, and magnetic resonance imaging, to assess their short- and long-term distributions, along with their viability, proliferation and functional interaction with the host myocardium. This review details the strengths and limitations of the different cell labelling and imaging techniques and their potential application to the clinical realm. We also consider the broader, multifaceted utility of imaging throughout the cell therapy process, providing a discussion of its considerable value during cell delivery and its importance during the evaluation of cardiac outcomes in clinical studies.

Keywords

Stem cells Imaging Heart Magnetic resonance imaging Single photon emission computed tomography Positron emission tomography Tracking Delivery 

Notes

Acknowledgements

This work was supported by grant funding from NIH HL 88048 and the Mayo Foundation (MR-P). Dr. Psaltis is the recipient of an Overseas Biomedical Fellowship from the National Health and Medical Research Council of Australia and the Marjorie Hooper Overseas Fellowship from the Royal Australasian College of Physicians.

Conflicts of interest

None.

References

  1. 1.
    Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A. Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc 2009;84:876–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–17.PubMedCrossRefGoogle Scholar
  4. 4.
    Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Assmus B, Honold J, Schächinger V, Britten MB, Fischer-Rasokat U, Lehmann R, et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006;355:1222–32.PubMedCrossRefGoogle Scholar
  6. 6.
    Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006;355:1199–209.PubMedCrossRefGoogle Scholar
  7. 7.
    Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006;367:113–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circ Heart Fail 2009;2:417–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Menasché P, Alfieri O, Janssens S, McKenna W, Reichenspurner H, Trinquart L, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 2008;117:1189–200.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 2007;115:3165–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Lipinski MJ, Biondi-Zoccai GG, Abbate A, Khianey R, Sheiban I, Bartunek J, et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 2007;50:1761–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 2007;167:989–97.PubMedCrossRefGoogle Scholar
  14. 14.
    Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Holschermann H, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006;355:1210–21.PubMedCrossRefGoogle Scholar
  15. 15.
    Meyer GP, Wollert KC, Lotz J, Steffens J, Lippolt P, Fichtner S, et al. 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 2006;113:1287–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S. Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J 2007;28:766–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Brunskill SJ, Hyde CJ, Doree CJ, Watt SM, Martin-Rendon E. Route of delivery and baseline left ventricular ejection fraction, key factors of bone-marrow-derived cell therapy for ischaemic heart disease. Eur J Heart Fail 2009;11:887–96.PubMedCrossRefGoogle Scholar
  18. 18.
    Hou D, Youssef EA, Brinton TJ, Zhang P, Rogers P, Price ET, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;112:I150–6.PubMedGoogle Scholar
  19. 19.
    Hofmann M, Wollert KC, Meyer GP, Menke A, Arseniev L, Hertenstein B, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005;111:2198–202.PubMedCrossRefGoogle Scholar
  20. 20.
    Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-controlled study. Circ Res 2005;97:756–62.PubMedCrossRefGoogle Scholar
  21. 21.
    Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 2004;363:783–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Freyman T, Polin G, Osman H, Crary J, Lu M, Cheng L, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006;27:1114–22.PubMedCrossRefGoogle Scholar
  23. 23.
    Ly HQ, Hoshino K, Pomerantseva I, Kawase Y, Yoneyama R, Takewa Y, et al. In vivo myocardial distribution of multipotent progenitor cells following intracoronary delivery in a swine model of myocardial infarction. Eur Heart J 2009;30:2861–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Grossman PM, Han Z, Palasis M, Barry JJ, Lederman RJ. Incomplete retention after direct myocardial injection. Catheter Cardiovasc Interv 2002;55:392–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Perin EC, Silva GV, Assad JA, Vela D, Buja LM, Sousa AL, et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol 2008;44:486–95.PubMedCrossRefGoogle Scholar
  26. 26.
    Mitchell AJ, Sabondjian E, Sykes J, Deans L, Zhu W, Lu X, et al. Comparison of initial cell retention and clearance kinetics after subendocardial or subepicardial injections of endothelial progenitor cells in a canine myocardial infarction model. J Nucl Med 2010;51:413–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Poh KK, Sperry E, Young RG, Freyman T, Barringhaus KG, Thompson CA. Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem cells: safety of a high dose, “off-the-shelf”, cellular cardiomyoplasty strategy. Int J Cardiol 2007;117:360–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Psaltis PJ, Zannettino AC, Gronthos S, Worthley SG. Intramyocardial navigation and mapping for stem cell delivery. J Cardiovasc Transl Res 2010;3:135–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Ince H, Petzsch M, Rehders TC, Chatterjee T, Nienaber CA. Transcatheter transplantation of autologous skeletal myoblasts in postinfarction patients with severe left ventricular dysfunction. J Endovasc Ther 2004;11:695–704.PubMedCrossRefGoogle Scholar
  30. 30.
    Smits PC, Nienaber C, Colombo A, Ince H, Carlino M, Theuns DA, et al. Myocardial repair by percutaneous cell transplantation of autologous skeletal myoblast as a stand alone procedure in post myocardial infarction chronic heart failure patients. Eurointervention 2006;1:417–24.PubMedGoogle Scholar
  31. 31.
    de la Fuente LM, Stertzer SH, Argentieri J, Peñaloza E, Miano J, Koziner B, et al. Transendocardial autologous bone marrow in chronic myocardial infarction using a helical needle catheter: 1-year follow-up in an open-label, nonrandomized, single-center pilot study (the TABMMI study). Am Heart J 2007;154:79.e1–7.CrossRefGoogle Scholar
  32. 32.
    Duckers HJ, Houtgraaf J, Hehrlein C, Schofer J, Waltenberger J, Gershlick A, et al. Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial. Eurointervention 2011;6:805–12.PubMedCrossRefGoogle Scholar
  33. 33.
    Psaltis PJ, Worthley SG. Endoventricular electromechanical mapping-the diagnostic and therapeutic utility of the NOGA® XP Cardiac Navigation System. J Cardiovasc Transl Res 2009;2:48–62.PubMedCrossRefGoogle Scholar
  34. 34.
    Kornowski R, Hong MK, Gepstein L, Goldstein S, Ellahham S, Ben-Haim SA, et al. Preliminary animal and clinical experiences using an electromechanical endocardial mapping procedure to distinguish infarcted from healthy myocardium. Circulation 1998;98:1116–24.PubMedGoogle Scholar
  35. 35.
    Fuchs S, Kornowski R, Shiran A, Pierre A, Ellahham S, Leon MB. Electromechanical characterization of myocardial hibernation in a pig model. Coron Artery Dis 1999;10:195–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Botker HE, Lassen JF, Hermansen F, Wiggers H, Søgaard P, Kim WY, et al. Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy. Circulation 2001;103:1631–7.PubMedGoogle Scholar
  37. 37.
    Psaltis PJ, Carbone A, Leong DP, Lau DH, Nelson AJ, Kuchel T, et al. Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy. Int J Cardiovasc Imaging 2011;27:25–37.PubMedCrossRefGoogle Scholar
  38. 38.
    Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003;107:2294–302.PubMedCrossRefGoogle Scholar
  39. 39.
    Krause K, Jaquet K, Schneider C, Haupt S, Lioznov MV, Otte KM, et al. Percutaneous intramyocardial stem cell injection in patients with acute myocardial infarction: first-in-man study. Heart 2009;95:1145–52.PubMedCrossRefGoogle Scholar
  40. 40.
    Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, et al. Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC Cardiovasc Interv 2010;3:974–83.PubMedCrossRefGoogle Scholar
  41. 41.
    Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 2004;94:92–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Dib N, Menasche P, Bartunek JJ, Zeiher AM, Terzic A, Chronos NA, et al. Recommendations for successful training on methods of delivery of biologics for cardiac regeneration: a report of the International Society for Cardiovascular Translational Research. JACC Cardiovasc Interv 2010;3:265–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Fernandes MR, Silva GV, Zheng Y, Oliveira EM, Cardoso CO, Canales J, et al. Validation of QwikStar Catheter for left ventricular electromechanical mapping with NOGA XP system. Tex Heart Inst J 2008;35:240–4.PubMedGoogle Scholar
  44. 44.
    Perin EC, Silva GV, Fernandes MR, Munger T, Pandey A, Sehra R, et al. First experience with remote left ventricular mapping and transendocardial cell injection with a novel integrated magnetic navigation-guided electromechanical mapping system. Eurointervention 2007;3:142–8.PubMedGoogle Scholar
  45. 45.
    Wei H, Ooi TH, Tan G, Lim SY, Qian L, Wong P, et al. Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers. Heart Fail Rev 2010;15:1–14.PubMedCrossRefGoogle Scholar
  46. 46.
    Dick AJ, Guttman MA, Raman VK, Peters DC, Pessanha BS, Hill JM, et al. Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in swine. Circulation 2003;108:2899–904.PubMedCrossRefGoogle Scholar
  47. 47.
    Corti R, Badimon J, Mizsei G, Macaluso F, Lee M, Licato P, et al. Real time magnetic resonance guided endomyocardial local delivery. Heart 2005;91:348–53.PubMedCrossRefGoogle Scholar
  48. 48.
    Baklanov DV, de Muinck ED, Simons M, Moodie KL, Arbuckle BE, Thompson CA, et al. Live 3D echo guidance of catheter-based endomyocardial injection. Catheter Cardiovasc Interv 2005;65:340–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Cheng Y, Sherman W, Yi G, Conditt G, Sheehy A, Martens T, et al. Real time 3D echo guided intramyocardial delivery of mesenchymal precursor cells in a chronic myocardial infarct ovine model using a novel catheter. J Am Coll Cardiol 2009;53:A41.Google Scholar
  50. 50.
    Saeed M, Saloner D, Weber O, Martin A, Henk C, Higgins C. MRI in guiding and assessing intramyocardial therapy. Eur Radiol 2005;15:851–63.PubMedCrossRefGoogle Scholar
  51. 51.
    Horvath KA, Mazilu D, Kocaturk O, Li M. Transapical aortic valve replacement under real-time magnetic resonance imaging guidance: experimental results with balloon-expandable and self-expanding stents. Eur J Cardiothorac Surg 2011;39:822–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Fahrig R, Butts K, Wen Z, Saunders R, Kee ST, Sze DY, et al. Truly hybrid interventional MR/X-ray system: investigation of in vivo applications. Acad Radiol 2001;8:1200–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Vogl TJ, Balzer JO, Mack MG, Bett G, Oppelt A. Hybrid MR interventional imaging system: combined MR and angiography suites with single interactive table. Feasibility study in vascular liver tumor procedures. Eur Radiol 2002;12:1394–400.PubMedCrossRefGoogle Scholar
  54. 54.
    Liu CY, Farahani K, Lu DS, Duckwiler G, Oppelt A. Safety of MRI-guided endovascular guidewire applications. J Magn Reson Imaging 2000;12:75–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Lederman RJ, Guttman MA, Peters DC, Thompson RB, Sorger JM, Dick AJ, et al. Catheter-based endomyocardial injection with real-time magnetic resonance imaging. Circulation 2002;105:1282–4.PubMedGoogle Scholar
  56. 56.
    Karmarkar PV, Kraitchman DL, Izbudak I, Hofmann LV, Amado LC, Fritzges D, et al. MR-trackable intramyocardial injection catheter. Magn Reson Med 2004;51:1163–72.PubMedCrossRefGoogle Scholar
  57. 57.
    de Silva R, Gutiérrez LF, Raval AN, McVeigh ER, Ozturk C, Lederman RJ. X-ray fused with magnetic resonance imaging (XFM) to target endomyocardial injections: validation in a swine model of myocardial infarction. Circulation 2006;114:2342–50.PubMedCrossRefGoogle Scholar
  58. 58.
    Williams AR, Zambrano JP, Rodriguez J, Guerra D, Bonny G, McNiece I, et al. Merging three-dimensional cardiac MRI with electroanatomical mapping to guide transendocardial injections of mesenchymal stem cells. Circulation 2010;122:A15947.Google Scholar
  59. 59.
    Ladage D, Turnbull IC, Ishikawa K, Takewa Y, Rapti K, Morel C, et al. Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model. Gene Ther 2011; Published online April 21.Google Scholar
  60. 60.
    Azene NM, Ehtiati T, Fu Y, Flammang A, Guehring J, Gilson WD, et al. Intrapericardial delivery of visible microcapsules containing stem cells using xfm (x-ray fused with magnetic resonance imaging). J Cardiovasc Magn Reson 2011;13 Suppl 1:P26.CrossRefGoogle Scholar
  61. 61.
    Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003;108:1009–14.PubMedCrossRefGoogle Scholar
  62. 62.
    Stuckey DJ, Carr CA, Martin-Rendon E, Tyler DJ, Willmott C, Cassidy PJ, et al. Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart. Stem Cells 2006;24:1968–75.PubMedCrossRefGoogle Scholar
  63. 63.
    Chin BB, Nakamoto Y, Bulte JW, Pittenger MF, Wahl R, Kraitchman DL. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun 2003;24:1149–54.PubMedCrossRefGoogle Scholar
  64. 64.
    Silva SA, Sousa AL, Haddad AF, Azevedo JC, Soares VE, Peixoto CM, et al. Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: comparison of two delivery techniques. Cell Transplant 2009;18:343–52.PubMedCrossRefGoogle Scholar
  65. 65.
    Penicka M, Lang O, Widimsky P, Kobylka P, Kozak T, Vanek T, et al. One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction. Heart 2007;93:837–41.PubMedCrossRefGoogle Scholar
  66. 66.
    Goussetis E, Manginas A, Koutelou M, Peristeri I, Theodosaki M, Kollaros N, et al. Intracoronary infusion of CD133+ and CD133-CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution. Stem Cells 2006;24:2279–83.PubMedCrossRefGoogle Scholar
  67. 67.
    Kang WJ, Kang HJ, Kim HS, Chung JK, Lee MC, Lee DS. Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med 2006;47:1295–301.PubMedGoogle Scholar
  68. 68.
    Doyle B, Kemp BJ, Chareonthaitawee P, Reed C, Schmeckpeper J, Sorajja P, et al. Dynamic tracking during intracoronary injection of 18F-FDG-labeled progenitor cell therapy for acute myocardial infarction. J Nucl Med 2007;48:1708–14.PubMedCrossRefGoogle Scholar
  69. 69.
    de Waha S, Fuernau G, Eitel I, Lurz P, Desch S, Schuler G, et al. Measuring treatment effects in clinical trials using cardiac MRI. Curr Cardiovasc Imaging Rep 2011; Published online January 19.Google Scholar
  70. 70.
    Ye Y, Bogaert J. Cell therapy in myocardial infarction: emphasis on the role of MRI. Eur Radiol 2008;18:548–69.PubMedCrossRefGoogle Scholar
  71. 71.
    Wunderbaldinger P, Josephson L, Weissleder R. Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR contrast agents. Acad Radiol 2002;9 Suppl 2:S304–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Park KS, Tae J, Choi B, Kim YS, Moon C, Kim SH, et al. Characterization, in vitro cytotoxicity assessment, and in vivo visualization of multimodal, RITC-labeled, silica-coated magnetic nanoparticles for labeling human cord blood-derived mesenchymal stem cells. Nanomedicine 2010;6:263–76.PubMedCrossRefGoogle Scholar
  73. 73.
    Himes N, Min JY, Lee R, Brown C, Shea J, Huang X, et al. In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction. Magn Reson Med 2004;52:1214–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Küstermann E, Roell W, Breitbach M, Wecker S, Wiedermann D, Buehrle C, et al. Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation. NMR Biomed 2005;18:362–70.PubMedCrossRefGoogle Scholar
  75. 75.
    Amsalem Y, Mardor Y, Feinberg MS, Landa N, Miller L, Daniels D, et al. Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation 2007;116:I38–45.PubMedCrossRefGoogle Scholar
  76. 76.
    Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107:2290–3.PubMedCrossRefGoogle Scholar
  77. 77.
    Bulte JW, Kostura L, Mackay A, Karmarkar PV, Izbudak I, Atalar E, et al. Feridex-labeled mesenchymal stem cells: cellular differentiation and MR assessment in a canine myocardial infarction model. Acad Radiol 2005;12 Suppl 1:S2–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Terrovitis JV, Bulte JW, Sarvananthan S, Crowe LA, Sarathchandra P, Batten P, et al. Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on collagen scaffolds-relevance to tissue engineering. Tissue Eng 2006;12:2765–75.PubMedCrossRefGoogle Scholar
  79. 79.
    Stuckey DJ, Ishii H, Chen QZ, Boccaccini AR, Hansen U, Carr CA, et al. Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction. Tissue Eng Part A 2010;16:3395–402.PubMedCrossRefGoogle Scholar
  80. 80.
    Kanematsu M, Kondo H, Goshima S, Kato H, Tsuge U, Hirose Y, et al. Imaging liver metastases: review and update. Eur J Radiol 2006;58:217–28.PubMedCrossRefGoogle Scholar
  81. 81.
    Wu L, Cao Y, Liao C, Huang J, Gao F. Diagnostic performance of USPIO-enhanced MRI for lymph-node metastases in different body regions: a meta-analysis. Eur J Radiol 2010; Published online January 2.Google Scholar
  82. 82.
    de Vries IJ, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, et al. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 2005;23:1407–13.PubMedCrossRefGoogle Scholar
  83. 83.
    Zhu J, Zhou L, XingWu F. Tracking neural stem cells in patients with brain trauma. N Engl J Med 2006;355:2376–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Chen IY, Greve JM, Gheysens O, Willmann JK, Rodriguez-Porcel M, Chu P, et al. Comparison of optical bioluminescence reporter gene and superparamagnetic iron oxide MR contrast agent as cell markers for noninvasive imaging of cardiac cell transplantation. Mol Imaging Biol 2009;11:178–87.PubMedCrossRefGoogle Scholar
  85. 85.
    Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, et al. Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed 2005;18:553–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Suzuki Y, Zhang S, Kundu P, Yeung AC, Robbins RC, Yang PC. In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 2007;57:1173–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Yang JX, Tang WL, Wang XX. Superparamagnetic iron oxide nanoparticles may affect endothelial progenitor cell migration ability and adhesion capacity. Cytotherapy 2010;12:251–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Schäfer R, Kehlbach R, Müller M, Bantleon R, Kluba T, Ayturan M, et al. Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability. Cytotherapy 2009;11:68–78.PubMedCrossRefGoogle Scholar
  89. 89.
    Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004;17:513–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Bos C, Delmas Y, Desmoulière A, Solanilla A, Hauger O, Grosset C, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology 2004;233:781–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Terrovitis J, Stuber M, Youssef A, Preece S, Leppo M, Kizana E, et al. Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation 2008;117:1555–62.PubMedCrossRefGoogle Scholar
  92. 92.
    van den Bos EJ, Baks T, Moelker AD, Kerver W, van Geuns RJ, van der Giessen WJ, et al. Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking? Eur Heart J 2006;27:1620–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Mani V, Adler E, Briley-Saebo KC, Bystrup A, Fuster V, Keller G, et al. Serial in vivo positive contrast MRI of iron oxide-labeled embryonic stem cell-derived cardiac precursor cells in a mouse model of myocardial infarction. Magn Reson Med 2008;60:73–81.PubMedCrossRefGoogle Scholar
  94. 94.
    Zhou R, Idiyatullin D, Moeller S, Corum C, Zhang H, Qiao H, et al. SWIFT detection of SPIO-labeled stem cells grafted in the myocardium. Magn Reson Med 2010;63:1154–61.PubMedCrossRefGoogle Scholar
  95. 95.
    Tran LA, Krishnamurthy R, Muthupillai R, Cabreira-Hansen Mda G, Willerson JT, Perin EC, et al. Gadonanotubes as magnetic nanolabels for stem cell detection. Biomaterials 2010;31:9482–91.PubMedCrossRefGoogle Scholar
  96. 96.
    Adler ED, Bystrup A, Briley-Saebo KC, Mani V, Young W, Giovanonne S, et al. In vivo detection of embryonic stem cell-derived cardiovascular progenitor cells using Cy3-labeled Gadofluorine M in murine myocardium. JACC Cardiovasc Imaging 2009;2:1114–22.PubMedCrossRefGoogle Scholar
  97. 97.
    Partlow KC, Chen J, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, et al. 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J 2007;21:1647–54.PubMedCrossRefGoogle Scholar
  98. 98.
    Rodriguez-Porcel M, Brinton TJ, Chen IY, Gheysens O, Lyons J, Ikeno F, et al. Reporter gene imaging following percutaneous delivery in swine moving toward clinical applications. J Am Coll Cardiol 2008;51:595–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Terrovitis J, Lautamäki R, Bonios M, Fox J, Engles JM, Yu J, et al. Noninvasive quantification and optimization of acute cell retention by in vivo positron emission tomography after intramyocardial cardiac-derived stem cell delivery. J Am Coll Cardiol 2009;54:1619–26.PubMedCrossRefGoogle Scholar
  100. 100.
    Brenner W, Aicher A, Eckey T, Massoudi S, Zuhayra M, Koehl U, et al. 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med 2004;45:512–8.PubMedGoogle Scholar
  101. 101.
    Nowak B, Weber C, Schober A, Zeiffer U, Liehn EA, von Hundelshausen P, et al. Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells. Eur J Nucl Med Mol Imaging 2007;34:715–21.PubMedCrossRefGoogle Scholar
  102. 102.
    Gholamrezanezhad A, Mirpour S, Ardekani JM, Bagheri M, Alimoghadam K, Yarmand S, et al. Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect. Nucl Med Commun 2009;30:210–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Yoon JK, Park BN, Shim WY, Shin JY, Lee G, Ahn YH. In vivo tracking of 111In-labeled bone marrow mesenchymal stem cells in acute brain trauma model. Nucl Med Biol 2010;37:381–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Gildehaus FJ, Haasters F, Drosse I, Wagner E, Zach C, Mutschler W, et al. Impact of indium-111 oxine labelling on viability of human mesenchymal stem cells in vitro, and 3D cell-tracking using SPECT/CT in vivo. Mol Imaging Biol 2010; Published online November 17.Google Scholar
  105. 105.
    Huang J, Lee CC, Sutcliffe JL, Cherry SR, Tarantal AF. Radiolabeling rhesus monkey CD34+ hematopoietic and mesenchymal stem cells with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for microPET imaging. Mol Imaging 2008;7:1–11.PubMedGoogle Scholar
  106. 106.
    Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003;107:2134–9.PubMedCrossRefGoogle Scholar
  107. 107.
    Lyngbaek S, Ripa RS, Haack-Sørensen M, Cortsen A, Kragh L, Andersen CB, et al. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected 111In-labeled human mesenchymal stromal cells. Int J Cardiovasc Imaging 2010;26:273–84.PubMedCrossRefGoogle Scholar
  108. 108.
    Dedobbeleer C, Blocklet D, Toungouz M, Lambermont M, Unger P, Degaute JP, et al. Myocardial homing and coronary endothelial function after autologous blood CD34+ progenitor cells intracoronary injection in the chronic phase of myocardial infarction. J Cardiovasc Pharmacol 2009;53:480–5.PubMedCrossRefGoogle Scholar
  109. 109.
    Schächinger V, Aicher A, Döbert N, Röver R, Diener J, Fichtlscherer S, et al. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation 2008;118:1425–32.PubMedCrossRefGoogle Scholar
  110. 110.
    Seeger FH, Zeiher AM, Dimmeler S. Cell-enhancement strategies for the treatment of ischemic heart disease. Nat Clin Pract Cardiovasc Med 2007;4 Suppl 1:S110–3.PubMedCrossRefGoogle Scholar
  111. 111.
    Cao F, Lin S, Xie X, Ray P, Patel M, Zhang X, et al. In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation 2006;113:1005–14.PubMedCrossRefGoogle Scholar
  112. 112.
    Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 2009;120:408–16.PubMedCrossRefGoogle Scholar
  113. 113.
    Bhaumik S, Gambhir SS. Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci U S A 2002;99:377–82.PubMedCrossRefGoogle Scholar
  114. 114.
    Rodriguez-Porcel M, Gheysens O, Chen IY, Wu JC, Gambhir SS. Image-guided cardiac cell delivery using high-resolution small-animal ultrasound. Mol Ther 2005;12:1142–7.PubMedCrossRefGoogle Scholar
  115. 115.
    Wu JC, Chen IY, Sundaresan G, Min JJ, De A, Qiao JH, et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation 2003;108:1302–5.PubMedCrossRefGoogle Scholar
  116. 116.
    Terrovitis J, Kwok KF, Lautamäki R, Engles JM, Barth AS, Kizana E, et al. Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. J Am Coll Cardiol 2008;52:1652–60.PubMedCrossRefGoogle Scholar
  117. 117.
    Gilad AA, Winnard Jr PT, van Zijl PC, Bulte JW. Developing MR reporter genes: promises and pitfalls. NMR Biomed 2007;20:275–90.PubMedCrossRefGoogle Scholar
  118. 118.
    Naumova AV, Reinecke H, Yarnykh V, Deem J, Yuan C, Murry CE. Ferritin overexpression for noninvasive magnetic resonance imaging-based tracking of stem cells transplanted into the heart. Mol Imaging 2010;9:201–10.PubMedGoogle Scholar
  119. 119.
    Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003;17:545–80.PubMedCrossRefGoogle Scholar
  120. 120.
    Rodriguez-Porcel M. In vivo imaging and monitoring of transplanted stem cells: clinical applications. Curr Cardiol Rep 2010;12:51–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Terrovitis JV, Smith RR, Marbán E. Assessment and optimization of cell engraftment after transplantation into the heart. Circ Res 2010;106:479–94.PubMedCrossRefGoogle Scholar
  122. 122.
    Gyöngyösi M, Blanco J, Marian T, Trón L, Petneházy O, Petrasi Z, et al. Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circ Cardiovasc Imaging 2008;1:94–103.PubMedCrossRefGoogle Scholar
  123. 123.
    Kang JH, Lee DS, Paeng JC, Lee JS, Kim YH, Lee YJ, et al. Development of a sodium/iodide symporter (NIS)-transgenic mouse for imaging of cardiomyocyte-specific reporter gene expression. J Nucl Med 2005;46:479–83.PubMedGoogle Scholar
  124. 124.
    MacLaren DC, Gambhir SS, Satyamurthy N, Barrio JR, Sharfstein S, Toyokuni T, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 1999;6:785–91.PubMedCrossRefGoogle Scholar
  125. 125.
    Cohen B, Dafni H, Meir G, Harmelin A, Neeman M. Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors. Neoplasia 2005;7:109–17.PubMedCrossRefGoogle Scholar
  126. 126.
    Bengel FM, Anton M, Richter T, Simoes MV, Haubner R, Henke J, et al. Noninvasive imaging of transgene expression by use of positron emission tomography in a pig model of myocardial gene transfer. Circulation 2003;108:2127–33.PubMedCrossRefGoogle Scholar
  127. 127.
    Willmann JK, Paulmurugan R, Rodriguez-Porcel M, Stein W, Brinton TJ, Connolly AJ, et al. Imaging gene expression in human mesenchymal stem cells: from small to large animals. Radiology 2009;252:117–27.PubMedCrossRefGoogle Scholar
  128. 128.
    Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J, et al. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol 2009;6:53–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Li Z, Suzuki Y, Huang M, Cao F, Xie X, Connolly AJ, et al. Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells 2008;26:864–73.PubMedCrossRefGoogle Scholar
  130. 130.
    Qiao H, Zhang H, Zheng Y, Ponde DE, Shen D, Gao F, et al. Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection. Radiology 2009;250:821–9.PubMedCrossRefGoogle Scholar
  131. 131.
    Shen D, Liu D, Cao Z, Acton PD, Zhou R. Coregistration of magnetic resonance and single photon emission computed tomography images for noninvasive localization of stem cells grafted in the infarcted rat myocardium. Mol Imaging Biol 2007;9:24–31.PubMedCrossRefGoogle Scholar
  132. 132.
    Wang J, Zhang S, Rabinovich B, Bidaut L, Soghomonyan S, Alauddin MM, et al. Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circ Res 2010;106:1904–11.PubMedCrossRefGoogle Scholar
  133. 133.
    Catana C, Procissi D, Wu Y, Judenhofer MS, Qi J, Pichler BJ, et al. Simultaneous in vivo positron emission tomography and magnetic resonance imaging. Proc Natl Acad Sci U S A 2008;105:3705–10.PubMedCrossRefGoogle Scholar
  134. 134.
    Kuliszewski MA, Fujii H, Liao C, Smith AH, Xie A, Lindner JR, et al. Molecular imaging of endothelial progenitor cell engraftment using contrast-enhanced ultrasound and targeted microbubbles. Cardiovasc Res 2009;83:653–62.PubMedCrossRefGoogle Scholar
  135. 135.
    Barnett BP, Kraitchman DL, Lauzon C, Magee CA, Walczak P, Gilson WD, et al. Radiopaque alginate microcapsules for X-ray visualization and immunoprotection of cellular therapeutics. Mol Pharm 2006;3:531–8.PubMedCrossRefGoogle Scholar
  136. 136.
    Barnett BP, Ruiz-Cabello J, Hota P, Liddell R, Walczak P, Howland V, et al. Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology 2011;258:182–91.PubMedCrossRefGoogle Scholar
  137. 137.
    Penn MS. Stem-cell therapy after acute myocardial infarction: the focus should be on those at risk. Lancet 2006;367:87–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Bellenger NG, Burgess MI, Ray SG, Lahiri A, Coats AJ, Cleland JG, et al. 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 2000;21:1387–96.PubMedCrossRefGoogle Scholar
  139. 139.
    Arnesen H, Lunde K, Aakhus S, Forfang K. Cell therapy in myocardial infarction. Lancet 2007;369:2142–3.PubMedCrossRefGoogle Scholar
  140. 140.
    Schaefer A, Meyer GP, Fuchs M, Klein G, Kaplan M, Wollert KC, et al. Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial. Eur Heart J 2006;27:929–35.PubMedCrossRefGoogle Scholar
  141. 141.
    Assmus B, Rolf A, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail 2010;3:89–96.PubMedCrossRefGoogle Scholar
  142. 142.
    Aletras AH, Tilak GS, Natanzon A, Hsu LY, Gonzalez FM, Hoyt Jr RF, et al. 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 2006;113:1865–70.PubMedCrossRefGoogle Scholar
  143. 143.
    McCommis KS, O’Connor R, Lesniak D, Lyons M, Woodard PK, Gropler RJ, et al. Quantification of global myocardial oxygenation in humans: initial experience. J Cardiovasc Magn Reson 2010;12:34.PubMedCrossRefGoogle Scholar
  144. 144.
    Nahrendorf M, Sosnovik DE, French BA, Swirski FK, Bengel F, Sadeghi MM, et al. Multimodality cardiovascular molecular imaging, part II. Circ Cardiovasc Imaging 2009;2:56–70.PubMedCrossRefGoogle Scholar
  145. 145.
    Nahrendorf M, Sosnovik DE, Waterman P, Swirski FK, Pande AN, Aikawa E, et al. Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct. Circ Res 2007;100:1218–25.PubMedCrossRefGoogle Scholar
  146. 146.
    Hofstra L, Liem IH, Dumont EA, Boersma HH, van Heerde WL, Doevendans PA, et al. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet 2000;356:209–12.PubMedCrossRefGoogle Scholar
  147. 147.
    Kietselaer BL, Reutelingsperger CP, Boersma HH, Heidendal GA, Liem IH, Crijns HJ, et al. Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure. J Nucl Med 2007;48:562–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Narula J, Acio ER, Narula N, Samuels LE, Fyfe B, Wood D, et al. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat Med 2001;7:1347–52.PubMedCrossRefGoogle Scholar
  149. 149.
    Sosnovik DE, Schellenberger EA, Nahrendorf M, Novikov MS, Matsui T, Dai G, et al. Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn Reson Med 2005;54:718–24.PubMedCrossRefGoogle Scholar
  150. 150.
    Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, et al. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J Clin Invest 2004;113:1684–91.PubMedGoogle Scholar
  151. 151.
    Makowski MR, Ebersberger U, Nekolla S, Schwaiger M. In vivo molecular imaging of angiogenesis, targeting αvβ3 integrin expression, in a patient after acute myocardial infarction. Eur Heart J 2008;29:2201.PubMedCrossRefGoogle Scholar
  152. 152.
    Rodriguez-Porcel M, Cai W, Gheysens O, Willmann JK, Chen K, Wang H, et al. Imaging of VEGF receptor in a rat myocardial infarction model using PET. J Nucl Med 2008;49:667–73.PubMedCrossRefGoogle Scholar
  153. 153.
    Rodriguez-Porcel M. Non-invasive monitoring of angiogenesis in cardiology. Curr Cardiovasc Imaging Rep 2009;2:59–66.PubMedCrossRefGoogle Scholar
  154. 154.
    Psaltis PJ, Zannettino AC, Worthley SG, Gronthos S. Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells 2008;26:2201–10.PubMedCrossRefGoogle Scholar
  155. 155.
    Gyöngyösi M, Lang I, Dettke M, Beran G, Graf S, Sochor H, et al. Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study. Nat Clin Pract Cardiovasc Med 2009;6:70–81.PubMedCrossRefGoogle Scholar
  156. 156.
    Briguori C, Reimers B, Sarais C, Napodano M, Pascotto P, Azzarello G, et al. Direct intramyocardial percutaneous delivery of autologous bone marrow in patients with refractory myocardial angina. Am Heart J 2006;151:674–80.PubMedCrossRefGoogle Scholar
  157. 157.
    Beeres SL, Bax JJ, Dibbets P, Stokkel MP, Zeppenfeld K, Fibbe WE, et al. Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia. J Nucl Med 2006;47:574–80.PubMedGoogle Scholar
  158. 158.
    Fuchs S, Kornowski R, Weisz G, Satler LF, Smits PC, Okubagzi P, et al. Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease. Am J Cardiol 2006;97:823–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Tse HF, Thambar S, Kwong YL, Rowlings P, Bellamy G, McCrohon J, et al. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). Eur Heart J 2007;28:2998–3005.PubMedCrossRefGoogle Scholar
  160. 160.
    van Ramshorst J, Bax JJ, Beeres SL, Dibbets-Schneider P, Roes SD, Stokkel MP, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 2009;301:1997–2004.PubMedCrossRefGoogle Scholar
  161. 161.
    Dib N, Dinsmore J, Lababidi Z, White B, Moravec S, Campbell A, et al. One-year follow-up of feasibility and safety of the first U.S., randomized, controlled study using 3-dimensional guided catheter-based delivery of autologous skeletal myoblasts for ischemic cardiomyopathy (CAuSMIC study). JACC Cardiovasc Interv 2009;2:9–16.PubMedCrossRefGoogle Scholar
  162. 162.
    Kraitchman DL, Bulte JW. Imaging of stem cells using MRI. Basic Res Cardiol 2008;103:105–13.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Peter J. Psaltis
    • 1
  • Robert D. Simari
    • 1
  • Martin Rodriguez-Porcel
    • 1
  1. 1.Division of Cardiovascular Diseases, Department of Internal MedicineMayo ClinicRochesterUSA

Personalised recommendations