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Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment.

Methods and results

We studied acute(1 hour) cardiac/lung retention in 4 groups (n = 25) of rats (normal—NL, acute ischemia-reperfusion—AI-RM, acute permanent ligation—PL, and chronic infarct by ischemia-reperfusion—CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n = 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n = 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs 12.0% ± 3.9% vs 9.9 ± 2.8 vs 15.4% ± 5.5%; P = NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection.

Conclusions

Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.

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Acknowledgments

We are grateful to Dana Kemmer for administrative assistance, Michelle Leppo, BS and Junaid M. Afzal, MBBS, MS for help with experiments.

Disclosures

Dr. Eduardo Marbán is founder and equity holder of Capricor, Inc. that works on CDCs. Capricor provided no funding for the present study. The remaining authors report no conflicts.

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Authors and Affiliations

  1. Johns Hopkins University, 720 Rutland Ave, Ross 871, Baltimore, MD, 21210, USA

    Michael Bonios MD, John Terrovitis MD, Connie Y. Chang MSE, James M. Engles MS, MBA, Takahiro Higuchi MD, PhD, Riikka Lautamäki MD, Jianhua Yu BS, James Fox BS, Martin Pomper MD, PhD, Richard L. Wahl MD, Benjamin M. Tsui PhD, Brian O’Rourke MD, PhD, Frank M. Bengel MD & M. Roselle Abraham MD

  2. Cedars-Sinai Heart Institute, Los Angeles, CA, USA

    Eduardo Marbán MD, PhD

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  1. Michael Bonios MD
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  2. John Terrovitis MD
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  3. Connie Y. Chang MSE
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  4. James M. Engles MS, MBA
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  5. Takahiro Higuchi MD, PhD
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  14. Eduardo Marbán MD, PhD
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  15. M. Roselle Abraham MD
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Corresponding author

Correspondence to M. Roselle Abraham MD.

Additional information

Michael Bonios and John Terrovitis equally contributed to this work.

This study was supported by the WW Smith Foundation (West Conshohocken, PA) (MRA), Donald W Reynolds Foundation (Las Vegas, NV), AHA (Dallas, TX) (MRA), Maryland TEDCO (Columbia, MD) (MRA), NIH RO1 HL092985 (Bethesda, MD) (MRA and FB).

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Bonios, M., Terrovitis, J., Chang, C.Y. et al. Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution of cardiosphere-derived cells. J. Nucl. Cardiol. 18, 443–450 (2011). https://doi.org/10.1007/s12350-011-9369-9

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  • DOI: https://doi.org/10.1007/s12350-011-9369-9

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