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


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.
Gyöngyösi
Mariann
M
Department of Cardiology, Medical University of Vienna, Wahringer Gurtel 18-20, Vienna, Austria. mariann.gyongyosi@meduniwien.ac.at
Blanco
Jeronimo
J
Marian
Teréz
T
Trón
Lajos
L
Petneházy
Ors
O
Petrasi
Zsolt
Z
Hemetsberger
Rayyan
R
Rodriguez
Julio
J
Font
Gusztáv
G
Pavo
Imre J
IJ
Kertész
István
I
Balkay
László
L
Pavo
Noemi
N
Posa
Aniko
A
Emri
Miklos
M
Galuska
László
L
Kraitchman
Dara L
DL
Wojta
Johann
J
Huber
Kurt
K
Glogar
Dietmar
D
D000818:Animals; D005462:Fluorine Radioisotopes; D015870:Gene Expression; D017930:Genes, Reporter; D006147:Guanine / Q000031:analogs & derivatives; D006321:Heart / Q000000981:diagnostic imaging*; D007267:Injections; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D049268:Positron-Emission Tomography; D034421:Sus scrofa; D014162:Transfection; D019076:Transgenes
C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D005462:Fluorine Radioisotopes; D006147:Guanine