Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression.

Mariann Gyöngyösi, Jeronimo Blanco, Teréz Marian, Lajos Trón, Ors Petneházy, Zsolt Petrasi, Rayyan Hemetsberger, Julio Rodriguez, Gusztáv Font, Imre J. Pavo, István Kertész, László Balkay, Noemi Pavo, Aniko Posa, Miklos Emri, László Galuska, Dara L. Kraitchman, Johann Wojta, Kurt Huber, Dietmar Glogar

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate. METHODS AND RESULTS: A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30+/-2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3+/-1.5% versus 30.2+/-3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8+/-1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically. CONCLUSIONS: Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.

Original languageEnglish (US)
Pages (from-to)94-103
Number of pages10
JournalCirculation. Cardiovascular imaging
Volume1
Issue number2
DOIs
StatePublished - Sep 2008
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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    Gyöngyösi, M., Blanco, J., Marian, T., Trón, L., Petneházy, O., Petrasi, Z., Hemetsberger, R., Rodriguez, J., Font, G., Pavo, I. J., Kertész, I., Balkay, L., Pavo, N., Posa, A., Emri, M., Galuska, L., Kraitchman, D. L., Wojta, J., Huber, K., & Glogar, D. (2008). Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression. Circulation. Cardiovascular imaging, 1(2), 94-103. https://doi.org/10.1161/CIRCIMAGING.108.797449