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European Heart Journal Advance Access published online on August 17, 2009

European Heart Journal, doi:10.1093/eurheartj/ehp322
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

In vivo myocardial distribution of multipotent progenitor cells following intracoronary delivery in a swine model of myocardial infarction

Hung Q. Ly1,4,*, Kozo Hoshino1, Irina Pomerantseva3,1, Yoshiaki Kawase1, Ryuichi Yoneyama1, Yoshiaki Takewa1, Annik Fortier4, Summer L. Gibbs-Strauss2, Carrie Vooght2, John V. Frangioni2 and Roger J. Hajjar1

1 Mount Sinai School of Medicine, New York, NY, USA
2 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
3 Massuchetts General Hospital, Harvard Medical School, Boston, MA, USA
4 Department of Medicine, Montreal Heart Institute, Université de Montréal, 5000 Belanger Street (east), Montréal, QC, Canada

Received 21 July 2008; revised 16 June 2009; accepted 24 July 2009 * Corresponding author. Tel: +1 514 376 3330, Fax: +1 514 376 6299, Email: hung.ly{at}icm-mhi.org

Aims: There are few data comparing the fate of multipotent progenitor cells (MPCs) used in cardiac cell therapy after myocardial infarction (MI). To document in vivo distribution of MPCs delivered by intracoronary (IC) injection.

Methods and results: Using an anterior MI swine model, near-infrared (NIR) fluorescence was used for in vivo tracking of labelled MPCs [mesenchymal stromal (MSCs), bone marrow mononuclear (BMMNCs), and peripheral blood mononuclear (PBMNCs)] cells early after IC injection. Signal intensity ratios (SIRs) of injected over non-injected (reference) zones were used to report NIR fluorescence emission. Following IC injection, significant differences in mean SIR were documented when MSCs were compared with BMMNCs [1.28 ± 0.10 vs. 0.77 ± 0.11, P < 0.001; 95% CI (0.219, 0.805), respectively] or PBMNCs [1.28 ± 0.10 vs. 0.80 ± 0.14, P = 0.005; 95% CI (0.148, 0.813), respectively]. Differences were maintained during the 60 min tracking period, with only the MSC-injected groups continuously emitting NIR fluorescence (SIR>1). This is correlated with greater cell retention for MSCs relative to mononuclear cells. However, there was evidence of MSC-related vessel plugging in some swine.

Conclusion: Our in vivo NIR fluorescence findings suggest that MPC distribution and retention immediately after intracoronary delivery vary depending on cell population and could potentially impact the clinical efficacy of cardiac cell therapy.

Key Words: In vivo • Multipotent progenitor cells • Intracoronary • Myocardial infarction • Near-infrared fluorescence


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