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Current Cardiovascular Imaging Reports

, Volume 3, Issue 2, pp 106–112 | Cite as

Molecular Imaging of Stem Cell Transplantation in Myocardial Disease

  • Jaehoon Chung
  • Phillip C. Yang
Article

Abstract

Stem cell therapy has been heralded as a novel therapeutic option for cardiovascular disease. In vivo molecular imaging has emerged as an indispensible tool in investigating stem cell biology post-transplantation into the myocardium and in evaluating the therapeutic efficacy. This review highlights the features of each molecular imaging modality and discusses how these modalities have been applied to evaluate stem cell therapy.

Keywords

Stem cells Molecular imaging Heart disease 

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Wollert KC, Meyer GP, Lotz J, et al.: Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004, 364:141–148.CrossRefPubMedGoogle Scholar
  2. 2.
    Stamm C, Kleine HD, Westphal B, et al.: CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg 2004, 52:152–158.CrossRefPubMedGoogle Scholar
  3. 3.
    Assmus B, Schachinger V, Teupe C, et al.: Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 2002, 106:3009–3017.CrossRefPubMedGoogle Scholar
  4. 4.
    Perin EC, Dohmann HF, Borojevic R, et al.: Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003, 107:2294–2302.CrossRefPubMedGoogle Scholar
  5. 5.
    Orlic D, Kajstura J, Chimenti S, et al.: Bone marrow cells regenerate infarcted myocardium. Nature 2001, 410:701–705.CrossRefPubMedGoogle Scholar
  6. 6.
    Nygren JM, Jovinge S, Breitbach M, et al.: Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004, 10:494–501.CrossRefPubMedGoogle Scholar
  7. 7.
    Murry CE, Soonpaa MH, Reinecke H, et al.: Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004, 428:664–668.CrossRefPubMedGoogle Scholar
  8. 8.
    Laflamme MA, Chen KY, Naumova AV, et al.: Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007, 25:1015–1024.CrossRefPubMedGoogle Scholar
  9. 9.
    Liang HD, Blomley MJ: The role of ultrasound in molecular imaging. Br J Radiol 2003, 76:S140–S150.CrossRefPubMedGoogle Scholar
  10. 10.
    Morawski AM, Lanza GA, Wickline SA: Targeted contrast agents for magnetic resonance imaging and ultrasound. Curr Opin Biotechnol 2005, 16:89–92.CrossRefPubMedGoogle Scholar
  11. 11.
    Villanueva FS, Jankowski RJ, Klibanov S, et al.: Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. Circulation 1998, 98:1–5.PubMedGoogle Scholar
  12. 12.
    Demos SM, Dagar S, Klegerman M, et al.: In vitro targeting of acoustically reflective immunoliposomes to fibrin under various flow conditions. J Drug Target 1998, 5:507–518.CrossRefPubMedGoogle Scholar
  13. 13.
    Bara C, Ghodsizad A, Niehaus M, et al.: In vivo echocardiographic imaging of transplanted human adult stem cells in the myocardium labeled with clinically applicable CliniMACS nanoparticles. J Am Soc Echocardiogr 2006, 19:563–568.CrossRefPubMedGoogle Scholar
  14. 14.
    Aicher A, Brenner W, Zuhayra M, et al.: Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003, 107:2134–2139.CrossRefPubMedGoogle Scholar
  15. 15.
    Hofmann M, Wollert KC, Meyer GP, et al.: Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005, 111:2198–2202.CrossRefPubMedGoogle Scholar
  16. 16.
    Cao F, Lin S, Xie X, et al.: In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation 2006, 113:1005–1014.CrossRefPubMedGoogle Scholar
  17. 17.
    Cao YA, Wagers AJ, Beilhack A, et al.: Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci U S A 2004, 101:221–226.CrossRefPubMedGoogle Scholar
  18. 18.
    • Hendry SL 2nd, van der Bogt KE, Sheikh AY, et al.: Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells. J Thorac Cardiovasc Surg 2008, 136:1028–1037; e1021. This study shows significance of transplanted cell viability to get therapeutic benefit.CrossRefPubMedGoogle Scholar
  19. 19.
    Hung TC, Suzuki Y, Urashima T, et al.: Multimodality evaluation of the viability of stem cells delivered into different zones of myocardial infarction. Circ Cardiovasc Imaging 2008, 1:6–13.CrossRefPubMedGoogle Scholar
  20. 20.
    Massoud TF, Singh A, Gambhir SS: Noninvasive molecular neuroimaging using reporter genes: part II, experimental, current, and future applications. AJNR Am J Neuroradiol 2008, 29:409–418.CrossRefPubMedGoogle Scholar
  21. 21.
    Bulte JW, Douglas T, Witwer B, et al.: Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 2001, 19:1141–1147.CrossRefPubMedGoogle Scholar
  22. 22.
    Aikawa E, Nahrendorf M, Sosnovik D, et al.: Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation 2007, 115:377–386.CrossRefPubMedGoogle Scholar
  23. 23.
    Schellenberger EA, Hogemann D, Josephson L, et al.: Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Acad Radiol 2002, 9(Suppl 2):S310–S311.CrossRefPubMedGoogle Scholar
  24. 24.
    • Suzuki Y, Zhang S, Kundu P, et al.: In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med 2007, 57:1173–1179. This study shows SPIO labeling of stem cells does not affect the viability of cells.CrossRefPubMedGoogle Scholar
  25. 25.
    Kostura L, Kraitchman DL, Mackay AM, et al.: Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004, 17:513–517.CrossRefPubMedGoogle Scholar
  26. 26.
    Arai T, Kofidis T, Bulte JW, et al.: Dual in vivo magnetic resonance evaluation of magnetically labeled mouse embryonic stem cells and cardiac function at 1.5 t. Magn Reson Med 2006, 55:203–209.CrossRefPubMedGoogle Scholar
  27. 27.
    • Chen IY, Greve JM, Gheysens O, 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, 11:178–187. This study demonstrates SPIO direct labeling does not tell viability of transplanted cells.CrossRefPubMedGoogle Scholar
  28. 28.
    Kraitchman DL, Heldman AW, Atalar E, et al.: In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003, 107:2290–2293.CrossRefPubMedGoogle Scholar
  29. 29.
    Lin YJ, Koretsky AP: Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn Reson Med 1997, 38:378–388.CrossRefPubMedGoogle Scholar
  30. 30.
    • Yamada M, Gurney PT, Chung J, et al.: Manganese-guided cellular MRI of human embryonic stem cell and human bone marrow stromal cell viability. Magn Reson Med 2009, 62:1047–1054. This study shows manganese labeling of stem cells does not affect biologic property of human embryonic and mesenchymal stem cells.CrossRefPubMedGoogle Scholar
  31. 31.
    Bruvold M, Nordhoy W, Anthonsen HW, et al.: Manganese-calcium interactions with contrast media for cardiac magnetic resonance imaging: a study of manganese chloride supplemented with calcium gluconate in isolated Guinea pig hearts. Invest Radiol 2005, 40:117–125.CrossRefPubMedGoogle Scholar
  32. 32.
    Bulte JW, Zhang S, van Gelderen P, et al.: Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A 1999, 96:15256–15261.CrossRefPubMedGoogle Scholar
  33. 33.
    So PW, Hotee S, Herlihy AH, et al.: Generic method for imaging transgene expression. Magn Reson Med 2005, 54:218–221.CrossRefPubMedGoogle Scholar
  34. 34.
    Weissleder R, Tung CH, Mahmood U, et al.: In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999, 17:375–378.CrossRefPubMedGoogle Scholar
  35. 35.
    • Chung J, Kee K, Rajesh D, et al.: In vivo molecular MRI of embryonic stem cell survival kinetics following transplantation into murine injured myocardium. Circulation 2009, 120:A32. This is the first study to show in vivo viability of embryonic stem cells using an MRI reporter gene.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Medicine, Division of Cardiovascular MedicineStanford University School of MedicineStanfordUSA

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