Skip to main content
Log in

Cell-based therapies and imaging in cardiology

  • Supplement
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Cell therapy for cardiac repair has emerged as one of the most exciting and promising developments in cardiovascular medicine. Evidence from experimental and clinical studies is increasing that this innovative treatment will influence clinical practice in the future. But open questions and controversies with regard to the basic mechanisms of this therapy continue to exist and emphasise the need for specific techniques to visualise the mechanisms and success of therapy in vivo. Several non-invasive imaging approaches which aim at tracking of transplanted cells in the heart have been introduced. Among these are direct labelling of cells with radionuclides or paramagnetic agents, and the use of reporter genes for imaging of cell transplantation and differentiation. Initial studies have suggested that these molecular imaging techniques have great potential. Integration of cell imaging into studies of cardiac cell therapy holds promise to facilitate further growth of the field towards a broadly clinically useful application.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Forrester JS, Price MJ, Makkar RR. Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation 2003;108:1139–45

    Article  PubMed  Google Scholar 

  2. Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation 2004;109:2692–7

    Article  PubMed  Google Scholar 

  3. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–5

    Article  PubMed  Google Scholar 

  4. Murry CE, Soonpaa MH, Reinecke H, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004;428:664–8

    Article  PubMed  Google Scholar 

  5. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–8

    Article  PubMed  Google Scholar 

  6. Assmus B, Schachinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002;106:3009–17

    Article  PubMed  Google Scholar 

  7. 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;364:141–8

    Article  PubMed  Google Scholar 

  8. Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood 1998;92:362–7

    PubMed  Google Scholar 

  9. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964–7

    Google Scholar 

  10. Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001;107:1395–402

    Google Scholar 

  11. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430–6

    Article  PubMed  Google Scholar 

  12. Urbich C, Heeschen C, Aicher A, et al. Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat Med 2005;11:206–13

    Article  PubMed  Google Scholar 

  13. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002;105:93–8

    Article  PubMed  Google Scholar 

  14. Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z. Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 2003;108:2070–3

    Article  PubMed  Google Scholar 

  15. Badorff C, Brandes RP, Popp R, et al. Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation 2003;107:1024–32

    Article  PubMed  Google Scholar 

  16. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004;428:668–73

    Article  PubMed  Google Scholar 

  17. 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

    Article  PubMed  Google Scholar 

  18. Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 2003;9:1195–201

    Article  PubMed  Google Scholar 

  19. Kawada H, Fujita J, Kinjo K, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood 2004;104:3581–7

    Article  PubMed  Google Scholar 

  20. Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005;11:367–8

    Article  PubMed  Google Scholar 

  21. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003;114:763–76

    Article  PubMed  Google Scholar 

  22. Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 2003;100:12313–8

    Article  PubMed  Google Scholar 

  23. Laugwitz KL, Moretti A, Lam J, et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005;433:647–53

    Article  PubMed  Google Scholar 

  24. Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004;95:911–21

    Article  PubMed  Google Scholar 

  25. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 2004;110:349–55

    Article  PubMed  Google Scholar 

  26. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002;13:4279–95

    Google Scholar 

  27. Kehat I, Kenyagin-Karsenti D, Snir M, et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 2001;108:407–14

    Google Scholar 

  28. Hwang WS, Roh SI, Lee BC, et al. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science 2005;308:1777–83

    Article  PubMed  Google Scholar 

  29. Britten MB, Abolmaali ND, Assmus B, et al. 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 2003;108:2212–8

    Article  PubMed  Google Scholar 

  30. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004;44:1690–9

    Article  PubMed  Google Scholar 

  31. Fernandez-Aviles F, San Roman JA, Garcia-Frade J, et al. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 2004;95:742–8

    Article  PubMed  Google Scholar 

  32. Chen SL, Fang WW, Ye F, 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

    Article  PubMed  Google Scholar 

  33. Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003;361:47–9

    Article  PubMed  Google Scholar 

  34. Fuchs S, Satler LF, Kornowski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 2003;41:1721–4

    Article  PubMed  Google Scholar 

  35. Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 2003;107:2294–302

    Article  PubMed  Google Scholar 

  36. Perin EC, Dohmann HF, Borojevic R, et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004;110:II213–8

    Article  PubMed  Google Scholar 

  37. Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 2003;361:45–6

    Article  PubMed  Google Scholar 

  38. Hamano K, Nishida M, Hirata K, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 2001;65:845–7

    Article  PubMed  Google Scholar 

  39. Galinanes M, Loubani M, Davies J, Chin D, Pasi J, Bell PR. Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans. Cell Transplant 2004;13:7–13

    PubMed  Google Scholar 

  40. Janssens S, Dubois C, Dens J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: a double-blind, randomized, and placebo-controlled clinical trial. J Am Coll Cardiol 2005;Suppl (abstract)

  41. Vanderheyden M, Mansour S, Vandekerckhove B, et al. Selected intracoronary CD133+ bone marrow cells promote cardiac regeneration after acute myocardial infarction. Circulation 2004;Suppl (abstract)

  42. Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17:484–99

    Article  PubMed  Google Scholar 

  43. Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003;108:1009–14

    Article  PubMed  Google Scholar 

  44. Kraitchman DL, Heldman AW, Atalar E, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation 2003;107:2290–3

    Article  PubMed  Google Scholar 

  45. Aicher A, Brenner W, Zuhayra M, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003;107:2134–9

    Article  PubMed  Google Scholar 

  46. Brenner W, Aicher A, Eckey T, et al. 111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model. J Nucl Med 2004;45:512–8

    PubMed  Google Scholar 

  47. 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

    Article  PubMed  Google Scholar 

  48. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003;108:863–8

    Article  PubMed  Google Scholar 

  49. Hofmann M, Wollert KC, Meyer GP, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005;111:2198–202

    Article  PubMed  Google Scholar 

  50. Bulte JW, Kraitchman DL, Mackay AM, Pittenger MF. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 2004;104:3410–2; author reply 3412–3

    Article  PubMed  Google Scholar 

  51. Bengel FM, Anton M, Avril N, et al. Uptake of radiolabeled 2′-fluoro-2′-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil in cardiac cells after adenoviral transfer of the herpesvirus thymidine kinase gene: the cellular basis for cardiac gene imaging. Circulation 2000;102:948–50

    PubMed  Google Scholar 

  52. Wu JC, Inubushi M, Sundaresan G, Schelbert HR, Gambhir SS. Positron emission tomography imaging of cardiac reporter gene expression in living rats. Circulation 2002;106:180–3

    Article  PubMed  Google Scholar 

  53. Wu JC, Chen IY, Sundaresan G, et al. Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography. Circulation 2003;108:1302–5

    Article  PubMed  Google Scholar 

  54. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci U S A 2001;98:9300–5

    Article  PubMed  Google Scholar 

  55. Miyagawa M, Beyer M, Wagner B, et al. Cardiac reporter gene imaging using the human sodium/iodide symporter gene. Cardiovasc Res 2005;65:195–202

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank M. Bengel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bengel, F.M., Schachinger, V. & Dimmeler, S. Cell-based therapies and imaging in cardiology. Eur J Nucl Med Mol Imaging 32 (Suppl 2), S404–S416 (2005). https://doi.org/10.1007/s00259-005-1898-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-005-1898-5

Keywords

Navigation