Advances in cardiovascular molecular imaging for tracking stem cell therapy

Katherine J. Ransohoff; Joseph C. Wu

doi:10.1160/TH09-08-0530

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(01): 13-22
DOI: 10.1160/TH09-08-0530

Theme Issue Article

Schattauer GmbH

Advances in cardiovascular molecular imaging for tracking stem cell therapy

Authors

Katherine J. Ransohoff

¹Department of Medicine (Division of Cardiology), Stanford University School of Medicine, Stanford, California, USA

²Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, California, USA
Joseph C. Wu

¹Department of Medicine (Division of Cardiology), Stanford University School of Medicine, Stanford, California, USA

²Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, California, USA

Abstract

PDF Download

Summary

The high mortality rate associated with cardiovascular disease is partially due to the lack of proliferative cells in the heart. Without adequate repair following myocardial infarction, progressive dilation can lead to heart failure. Stem cell therapies present one promising option for treating cardiovascular disease, though the specific mechanisms by which they benefit the heart remain unclear. Before stem cell therapies can be used safely in human populations, their biology must be investigated using innovative technologies such as multi-modality molecular imaging. The present review will discuss the basic principles, labelling techniques, clinical applications, and drawbacks associated with four major modalities: radionuclide imaging, magnetic resonance imaging, bioluminescence imaging, and fluorescence imaging.

Keywords

Stem cells - cell transplantation - imaging - radionuclide - magnetic resonance - bioluminescence - fluorescence

PDF (1137 kb)

References

References
1 Lloyd-Jones D, Adams R, Carnethon M. et al Heart disease and stroke statistics--2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119: 480-486.
2 Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature 2008; 451: 937-942.
3 Borchardt TB. Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man?. Thromb Haemost 2007; 98: 311-318.
4 Gorlach A. Vascular remodelling processes: cells, signals and their integration. Thromb Haemost 2007; 98: 919-921.
5 Menasche P, Alfieri O, Janssens S. et al The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 2008; 117: 1189-1200.
6 THomson JA, Itskovitz-Eldor J, Shapiro SS. et al Embryonic stem cell lines derived from human blastocytes. Science 1998; 282: 1145-1147.
7 Cao F, Wagner RA, Wilson KD. et al Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS ONE 2008; 03: e3474.
8 Lee AS, Tang C, Cao F. et al Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle 2009; 08: 2608-2612.
9 Tse WT, Pendleton JD, Beyer WM. et al Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75: 389-397.
10 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: 863-868.
11 Taupin P. OTI-010 Osiris Therapeutics/JCR Pharmaceuticals. Curr Opin Investig Drugs 2006; 07: 473-481.
12 Hare JM, Traverse JH, Henry TD. 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: 2277-2286.
13 Orlic D, Kajstura J, Chimenti S. et al Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-705.
14 Balsam LB, Wagers AJ, Christensen JL. et al Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004; 428: 668-673.
15 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.
16 van der Bogt KE, Sheikh AY, Schrepfer S. et al Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation 2008; 118 (Suppl. 14) (Suppl) S121-129.
17 Fuchs S, Baffour R, Zhou YF. et al Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 2001; 37: 1726-1732.
18 Janssens S, Dubois C, Bogaert J. et al Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. The Lancet 2006; 367: 113-121.
19 Lunde K, Solheim S, Aakhus S. et al Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 1199-1209.
20 Wollert KC, Meyer GP, Lotz J. et al Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. The Lancet 2004; 364: 141-148.
21 Meyer GP, Wollert KC, Lotz J. 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: 1287-1294.
22 Schachinger V, Erbs S, Elsasser A. et al Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355: 1210-1221.
23 Lipinski MJ, Biondi-Zoccai GGL, Abbate A. 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: 1761-1767.
24 Rosenzweig A. Cardiac cell therapy -- mixed results from mixed cells. N Engl J Med 2006; 355: 1274-1277.
25 Gorlach A. The response to cardiovascular injury: A field of emerging complexity. Thromb Haemost 2007; 98: 259-261.
26 Steffens S, Montecucco F, Mach F. The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury. Thromb Haemost 2009; 102: 240-247.
27 Hausenloy DJ. Signalling pathways in ischaemic postconditioning. Thromb Haemost 2009; 101: 626-634.
28 Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003; 17: 545-580.
29 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: 1302-1305.
30 Terrovitis J, Kwok KF, Lautamäki R. 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: 1652-1660.
31 Peters AM, Saverymuttu SH. The value of indium-labeled leucocytes in clinical practice. Blood Rev 1987; 01: 65-76.
32 Chin BB, Nakamoto Y, Bulte JW. et al 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun 2003; 24: 1149-1154.
33 Hofmann M, Wollert KC, Meyer GP. et al Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation 2005; 111: 2198-2202.
34 Gyöngyösi M BJ, Marian T, Tron L. et al Serial non-invasive in vivo positron em-mission tomographyc (PET) tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circulation: Cardiovasc Imag 2008; 01: 94-103.
35 Willmann JK, Paulmurugan R, Rodriguez-Porcel M. et al Imaging gene expression in human mesenchymal stem cells: from small to large animals. Radiology 2009; 252: 117-127.
36 Yaghoubi SS, Couto MA, Chen CC. et al Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. J Nucl Med 2006; 47: 706-715.
37 Yaghoubi SS, Jensen MC, Satyamurthy N. et al Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Prac Oncol 2009; 06: 53-58.
38 Wu JC, Spin JM, Cao F. et al Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation. Physiol Genomics 2006; 25: 29-38.
39 Wu JC, Cao F, Dutta S. et al Proteomic analysis of reporter genes for molecular imaging of transplanted embryonic stem cells. Proteomics 2006; 06: 6234-6249.
40 Modo M, Mellodew K, Cash D. et al Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. NeuroImage 2004; 21: 311-317.
41 Budde MD, Frank JA. Magnetic tagging of therapeutic cells for MRI. J Nucl Med 2009; 50: 171-174.
42 Morawski AM, Winter PM, Crowder KC. et al Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Res Med 2004; 51: 480-486.
43 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.
44 Arbab AS, Yocum GT, Rad AM. 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: 553-559.
45 Gilad AA, Winnard Jr PT, van Zijl PC. et al Developing MR reporter genes: promises and pitfalls. NMR Biomed 2007; 20: 275-290.
46 Louie AY, Huber MM, Ahrens ET. et al In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotech 2000; 18: 321-325.
47 Cohen B, Dafni H, Meir G. et al Ferritin as an endogenous MRI reporter for non-invasive imaging of gene expression in C6 glioma tumors. Neoplasia 2005; 07: 109-117.
48 Basilion JP, Kennedy MC, Beinert H. et al Overexpression of iron-responsive element-binding protein and its analytical characterization as the RNA-bin-ding form, devoid of an iron-sulfur cluster. Arch Biochem Biophys 1994; 311: 517-522.
49 Weissleder R, Moore A, Mahmood U. et al In vivo magnetic resonance imaging of transgene expression. Nat Med 2000; 06: 351-354.
50 Beeres SLMA, Bengel FM, Bartunek J. et al Role of imaging in cardiac stem cell therapy. J Am Coll Cardiol 2007; 49: 1137-1148.
51 Shapiro EM, Sharer K, Skrtic S. et al In vivo detection of single cells by MRI. Magn Res Med 2006; 55: 242-249.
52 Li Z, Suzuki Y, Huang M. 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: 864-873.
53 Au K-W, Liao S-Y, Lee Y-K. et al Effects of iron oxide nanoparticles on cardiac differentiation of embryonic stem cells. Biochemical and Biophysical Research Communications 2009; 379: 898-903.
54 Sierra M, Machado C. Magnetic resonance imaging in patients with implantable cardiac devices. Rev Cardiovasc Med 2008; 09: 232-238.
55 Zhang SJ, Wu JC. Comparison of imaging techniques for tracking cardiac stem cell therapy. J Nucl Med 2007; 48: 3.
56 Bhaumik S, Gambhir SS. Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci USA 2002; 99: 377-382.
57 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.
58 Swijnenburg R-J, Schrepfer S, Cao F. et al In vivo imaging of embryonic stem cells reveals patterns of survival and immune rejection following transplantation. Stem Cells Devel 2008; 17: 1023-1030.
59 Hwang D, Kang J, Jeong J. et al Noninvasive in vivo monitoring of neuronal differentiation using reporter driven by a neuronal promoter. Eur J Nucl Med Mol Imag 2008; 35: 135-145.
60 Gruber PJ, Li Z, Li H. et al In vivo imaging of mlc2v-luciferase, a cardiac-specific reporter gene expression in mice1. Acad Radiol 2004; 11: 1022-1028.
61 Ntziachristos V, Ripoll J, Wang LV. et al Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotech 2005; 23: 313-320.
62 Krishnan M, Park JM, Cao F. et al Effects of epigenetic modulation on reporter gene expression: implications for stem cell imaging. FASEB J 2006; 20: 106-108.
63 Kang JH, Chung J-K. Molecular-genetic imaging based on reporter gene expression. J Nucl Med 2008; 49 (Suppl. 02) (Suppl) 164S-179.
64 Shaner NC, Steinbach PA, Tsien RY. A guide to choosing fluorescent proteins. Nat Meth 2005; 02: 905-909.
65 Graves EE, Ripoll J, Weissleder R. et al A submillimeter resolution fluorescence molecular imaging system for small animal imaging. Med Physics 2003; 30: 901-911.
66 Michalet X, Pinaud FF, Bentolila LA. et al Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005; 307: 538-544.
67 Lin S, Xie X, Patel M. et al Quantum dot imaging for embryonic stem cells. BMC Biotechnol 2007; 07: 67.
68 Sutton E, Henning T, Pichler B. et al Cell tracking with optical imaging. Eur Radiol 2008; 18: 2021-2032.
69 Tung C. Fluorescent peptide probes for in vivo diagnostic imaging. Peptide Science 2004; 76: 391-403.
70 Dubertret B, Skourides P, Norris DJ. et al In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 2002; 298: 1759-1762.
71 Schachinger V, Aicher A, Dobert N. et al Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation 2008; 118: 1425-1432.
72 Zhu J, Zhou L, XingWu F. Tracking neural stem cells in patients with brain trauma. N Engl J Med 2006; 355: 2376-2378.