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Cardiovascular Research Advance Access originally published online on November 13, 2007
Cardiovascular Research 2008 77(3):534-543; doi:10.1093/cvr/cvm071
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation

Sandra Burghoff1,, Zhaoping Ding1, Stefanie Gödecke1, Alexander Assmann1, Andreas Wirrwar2, Doris Buchholz2, Olga Sergeeva3, Cordula Leurs4, Helmut Hanenberg4, Hans-Wilhelm Müller2, Wilhelm Bloch5 and Jürgen Schrader1

1 Institute for Heart and Circulatory Physiology, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
2 Clinic for Nuclear Medicine, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
3 Department of Neurophysiology, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
4 Department of Pediatric Oncology Hematology and Immunology, Childrens Hospital, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany
5 Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany

*Corresponding author. Tel: +49 211 8112671; fax: +49 211 8112672. E-mail address: sandra.burghoff{at}uni-duesseldorf.de

Aims: Recent studies suggested that human umbilical vein endothelial cells (HUVECs) transdifferentiate into cardiomyocytes and smooth muscle cells in vitro. To test the functional relevance of this observation, we examined the transdifferentiation potential of HUVECs in vivo after intracoronary cell application in Wistar rats.

Methods and results: SPECT measurements (single photon emission computed tomography) revealed that 18% of 111In-labelled HUVECs infused by intracoronary delivery stably transplanted to the rat heart. For long-term tracking, HUVECs-expressing enhanced green fluorescent protein (EGFP) were infused. Two days following transplantation, HUVECs were positive for caspase-3. Within 3 days, EGFP was associated with individual cardiomyocytes. No labelling of endothelial and smooth muscle cells was observed. The total number of EGFP-labelled cardiomyocytes accounted for 58% of all initially trapped cells. These EGFP positive cells stained negatively for human mitochondrial proteins, but were positive for rat monocarboxylate transporter-1 protein (MCT-1). Furthermore, EGFP-mRNA was detected in these cells by single-cell RT–PCR (reverse transcription followed by polymerase chain reaction). After 21 days, EGFP positive cells were no longer observed. To investigate the underlying mechanism, we generated in vitro apoptotic bodies from EGFP-labelled HUVECs and found them to contain the genetic information for EGFP. Co-incubation of apoptotic bodies with neonatal rat cardiomyocytes caused cardiomyocytes to express EGFP.

Conclusion: When transplanted into the rat heart by efficient intracoronary delivery, EGFP-expressing HUVECs cause the exclusive but transient labelling of cardiomyocytes. Our in vivo findings suggest that it is not cell fusion and/or transdifferentiation that occurs under these conditions but rather a horizontal gene transfer of the EGFP marker via apoptotic bodies from endothelial cells to cardiomyocytes.

KEYWORDS Cell therapy; Transplantation; Stem cells; Catheter based stem cell transplantation; HUVECs; Horizontal gene transfer; Cardiac imaging; Multipinhole-SPECT

Time for primary review: 21 days


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