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Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model

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Abstract

Purpose

To establish PET as a tool for in-vivo quantification and monitoring of intramyocardially transplanted stem cells after labelling with FDG in mice with induced myocardial infarction.

Methods

After inducing myocardial infarction in C57BL/6 mice, murine embryonic stem cells were labelled with FDG and transplanted into the border zone of the infarction. Dynamic PET scans were acquired from 25 to 120 min after transplantation, followed by a scan with 20 MBq FDG administered intravenously for anatomical landmarking. All images were reconstructed using the OSEM 3D and MAP reconstruction algorithms. FDG data were corrected for cellular tracer efflux and used as marker for cellular retention. FACS analysis of transplanted cells expressing enhanced green fluorescent protein was performed to validate the PET data.

Results

We observed a rapid loss of cells from the site of transplantation, followed by stable retention over 120 min. Amounts of retention were 5.3 ± 1.1 % at 25 min, 5.0 ± 0.9 % at 60 min and 5.7 ± 1.2 % at 120 min. FACS analysis showed a high correlation without significant differences between the groups (P > 0.05). FDG labelling did not have any adverse effects on cell proliferation or differentiation.

Conclusion

Up-to-date imaging is a powerful method for tracking and quantifying intramyocardially transplanted stem cells in vivo in the mouse model. This revealed a massive cell loss within minutes, and thereafter a relatively stable amount of about 5 % remaining cells was observed. Our method may become crucial for further optimization of cardiac cell therapy in the widely used mouse model of infarction.

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Acknowledgments

We thank Christiane Groß, Barbara Markieton and Judith Arcifa for expert technical assistance. This work was supported by the FöFoLe Program of the LMU Munich (C.L. and W.M.F.), the BMBF (01GN0960 to R.D. and W.M.F.), and the Deutsche Forschungsgemeinschaft (DA 1296/2-1 to R.D. and FR 705/14-2 to W.M.F.). W.M.F. is the principal investigator of the Munich Heart Alliance.

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Authors and Affiliations

  1. Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, 18057, Rostock, Germany

    Cajetan Lang & Robert David

  2. Department of Nuclear Medicine, University of Munich, Munich, Germany

    Sebastian Lehner, Andrei Todica, Guido Boening & Peter Bartenstein

  3. Department of Cardiology, University of Munich, Marchioninistr. 15, 81377, Munich, Germany

    Wolfgang-Michael Franz

  4. Munich Heart Alliance, University of Munich, Munich, Germany

    Wolfgang-Michael Franz

  5. Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria

    Marcus Hacker

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  1. Cajetan Lang
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Correspondence to Robert David.

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Cajetan Lang and Sebastian Lehner contributed equally to this work.

Marcus Hacker and Robert David share the senior authorship.

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Lang, C., Lehner, S., Todica, A. et al. Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model. Eur J Nucl Med Mol Imaging 40, 1730–1738 (2013). https://doi.org/10.1007/s00259-013-2480-1

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