Cell and gene therapy with reporter gene imaging in myocardial ischemia.
Hell J Nucl Med
; 20(3): 198-203, 2017.
Article
en En
| MEDLINE
| ID: mdl-29177255
ABSTRACT
OBJECTIVE:
Reporter gene/probe systems have proved to be reliable for monitoring gene/cell therapy. We sought to evaluate whether a reporter gene/probe system, namely the human estrogen receptor ligand binding domain (hERL)/16α-18F fluoro-17ß-estradiol (18F-FES), could be used for monitoring vascular endothelial growth factor (VEGF) gene expression and response to bone marrow mesenchymal stem cell (MSCs) therapy in ischemic heart disease. ANIMALS ANDMETHODS:
Reporter gene hERL and therapeutic gene VEGF165 were linked through internal ribosome entry site (IRES), and then the recombinant adenovirus vector Adenovirus 5-hERL-IRES-VEGF (Ad5-EIV) was constructed and transfected into MSCs, and named Ad5-EIV-MSCs. Rat myocardial infarction was induced by coronary arterial branch ligature, and Ad5-EIV-MSCs were transplanted by injection into the peripheral myocardium, while non-transfected MSCs transplantation used as controls. Fluorine-18-FDG micro-PET imaging was performed to confirm myocardial infarction 1 day after surgery. Fluorine-18-FES micro-PET/CT images were acquired 2 days after Ad5-EIV-MSCs transplantation. Myocardial specimens were obtained and stained with hematoxylin-eosin (H&E) staining to verify the myocardial infarction. The expression of estrogen receptor (ER) and VEGF was detected using immunohistochemistry (IHC).RESULTS:
Rat myocardial infarction models were successfully produced and confirmed by H&E staining. Images of 18F-FDG PET showed obvious reduced or absent uptake of 18F-FDG on the infarct myocardium, while uniform and well-distribution on the normal myocardium. 18F-FES micro-PET/CT showed the tracer notable accumulated in the apical region where Ad5-EIV-MSCs were injected with an uptake value of 0.38±0.09%ID/g, which was much higher than that of surrounding normal myocardium with nearly no uptake of 18F-FES (0.10±0.03%ID/g, n=5, P<0.05). In the group of non-transfected MSCs, the apical uptake was similar to that of normal myocardium. Immunohistochemistry studies demonstrated positive expression of both ER and VEGF in the involved region accompanied by active angiogenesis.CONCLUSION:
This study confirmed that hERL/18F-FES could be used as a reporter gene/probe system for monitoring gene and cell therapy in the ischemic heart disease.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Isquemia Miocárdica
/
Genes Reporteros
/
Fluorodesoxiglucosa F18
/
Trasplante de Células Madre Mesenquimatosas
/
Tomografía Computarizada por Tomografía de Emisión de Positrones
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hell J Nucl Med
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2017
Tipo del documento:
Article
País de afiliación:
China