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Transcoronary delivery of bone marrow cells to the infarcted murine myocardium

Feasibility, cellular kinetics, and improvement in cardiac function

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Abstract

Efficient strategies for labelling and delivery of bone marrow derived stem cells (BMCs) are required to elucidate the cellular kinetics and therapeutic effects after BMC transfer for myocardial infarction (MI). Lineage negative (lin−) BMCs, labelled ex vivo in a simple procedure with the cell tracker dye tetramethyl-rhodamine (TAMRA), were reliably detected by fluorescence microscopy with higher specificity than retroviral enhanced green fluorescence protein (EGFP) marking and detection. Only few cells entered the ischemic myocardium after intravenous (i.v.) application, but this number increased more than 18-fold after transcoronary delivery. Time course and kinetic analysis over 12 h revealed that myocardial colonization seems to be a biphasic process of first order decay with different elimination half-lives. Most cells are eliminated rapidly during the first 2 h (t 1/2 40 min), but the remaining cells are retained significantly longer in the ischemic heart (t 1/2 5.2 h). In contrast, BMC colonization of the spleen increased rather in a linear fashion. Although transcoronary BMC transfusion did not alter infarct size, it increased capillary density in the infarct border zone and improved LV function 4 weeks after MI.

In conclusion, BMCs delivered by transcoronary injection increase capillary density and improve LV function after MI although homing to the ischemic heart is only transient.

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Acknowledgments

This work was supported by an early career grant from Hannover Medical School to C.T. (HiLF Program) and by the Herbert Quandt Foundation of the VARTA AG to D.K.

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Authors and Affiliations

  1. Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

    Christian Templin, Daniel Kotlarz, Frederik Marquart, Vanessa Brendecke, Arnd Schaefer, Tomasz Bonda, Denise Hilfiker-Kleiner, Helmut Drexler & Florian P. Limbourg

  2. Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany

    Frederik Marquart & Hassan Y. Naim

  3. Department of Vegetative Physiology and Pathophysiology, University of Hamburg, Hamburg, Germany

    Joerg Faulhaber

  4. Department of Dermatology Venereology and Allergology, University Medical Center Mannheim Ruprecht-Karls-University of Heidelberg , Mannheim, Germany

    Joerg Faulhaber

  5. Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

    Dimitrios Tsikas

  6. Department of Immunology, Hannover Medical School, Hannover, Germany

    Lars Ohl & Reinhold Foerster

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  1. Christian Templin
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Correspondence to Christian Templin.

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Templin, C., Kotlarz, D., Marquart, F. et al. Transcoronary delivery of bone marrow cells to the infarcted murine myocardium. Basic Res Cardiol 101, 301–310 (2006). https://doi.org/10.1007/s00395-006-0590-7

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  • DOI: https://doi.org/10.1007/s00395-006-0590-7

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