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

Sandra Burghoff, Zhaoping Ding, Stefanie Gödecke, Alexander Assmann, Andreas Wirrwar, Doris Buchholz, Olga Sergeeva, Cordula Leurs, Helmut Hanenberg, Hans Wilhelm Müller, Wilhelm Bloch, Jürgen Schrader

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)534-543
Number of pages10
JournalCardiovascular Research
Volume77
Issue number3
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Horizontal Gene Transfer
Cardiac Myocytes
Endothelial Cells
Transplantation
Human Umbilical Vein Endothelial Cells
Single-Photon Emission-Computed Tomography
Smooth Muscle Myocytes
enhanced green fluorescent protein
Cell Transdifferentiation
Cell Fusion
Mitochondrial Proteins
Caspase 3
Reverse Transcription
Wistar Rats

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Burghoff, S., Ding, Z., Gödecke, S., Assmann, A., Wirrwar, A., Buchholz, D., ... Schrader, J. (2008). Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation. Cardiovascular Research, 77(3), 534-543. https://doi.org/10.1093/cvr/cvm071

Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation. / Burghoff, Sandra; Ding, Zhaoping; Gödecke, Stefanie; Assmann, Alexander; Wirrwar, Andreas; Buchholz, Doris; Sergeeva, Olga; Leurs, Cordula; Hanenberg, Helmut; Müller, Hans Wilhelm; Bloch, Wilhelm; Schrader, Jürgen.

In: Cardiovascular Research, Vol. 77, No. 3, 02.2008, p. 534-543.

Research output: Contribution to journalArticle

Burghoff, S, Ding, Z, Gödecke, S, Assmann, A, Wirrwar, A, Buchholz, D, Sergeeva, O, Leurs, C, Hanenberg, H, Müller, HW, Bloch, W & Schrader, J 2008, 'Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation', Cardiovascular Research, vol. 77, no. 3, pp. 534-543. https://doi.org/10.1093/cvr/cvm071
Burghoff, Sandra ; Ding, Zhaoping ; Gödecke, Stefanie ; Assmann, Alexander ; Wirrwar, Andreas ; Buchholz, Doris ; Sergeeva, Olga ; Leurs, Cordula ; Hanenberg, Helmut ; Müller, Hans Wilhelm ; Bloch, Wilhelm ; Schrader, Jürgen. / Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation. In: Cardiovascular Research. 2008 ; Vol. 77, No. 3. pp. 534-543.
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abstract = "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.",
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AU - Gödecke, Stefanie

AU - Assmann, Alexander

AU - Wirrwar, Andreas

AU - Buchholz, Doris

AU - Sergeeva, Olga

AU - Leurs, Cordula

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AU - Müller, Hans Wilhelm

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