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Cardiovascular Research Advance Access [Accepted Manuscript] published online on November 13, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm071
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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
2 Clinic for Nuclear Medicine
3 Department of Neurophysiology
4 Department of Pediatric Oncology Hematology and Immunology, Childrens Hospital, Heinrich Heine University Duesseldorf, Germany
5 Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany

Corresponding author: Dr. rer.nat. S. Burghoff Heinrich Heine University Duesseldorf Institute for Heart and Circulatory Physiology Universitaetsstr. 1 40225 Duesseldorf Tel.: +49-211/8112671 Fax: +49-211/8112672 E-Mail: sandra.burghoff{at}uni-duesseldorf.de

Aim: 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 111indium oxine-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

Time for primary review: 21


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