Abstract
Introduction
Our objective was to trace and evaluate intracoronary transplanted mesenchymal stem
cells (MSCs) labelled with superparamagnetic iron oxide (SPIO) by using magnetic resonance
imaging (MRI) in a swine model of myocardial infarction (MI).
Methods
MSCs were transfected with a lentiviral vector carrying the gene encoding green fluorescent
protein (GFP) and labelled in vitro with SPIO. At 2 weeks after MI, swine were randomized
to intracoronary transplantation of dual-labelled MSCs (n = 10), MSC-GFP (n = 10),
and saline (n = 5). MRI examination was performed with a 1.5-T clinical scanner at
24 hours, 3 weeks, and 8 weeks after cell transplantation. Signal intensity changes,
cardiac function, and MI size were measured by means of MRI. The correlation between
MRI findings and histomorphologic findings was also investigated.
Results
MSCs could be efficiently and safely labelled with SPIO and GFP, and multipotentiality
was not affected, especially for cardiomyocyte-like cell differentiation. Signal intensity
on T2*-weighted imaging decreased substantially in the interventricular septum 24
hours after injection of MSCs. The intensity of hypointense signals appeared to increase
throughout the later time points. Both dual-labelled MSCs and MSC-GFP could dramatically
reduce the size of MI and improve cardiac function. Histologic data revealed that
cells positive for Prussian blue stain were found mainly in the border zone, which
also showed green fluorescence.
Conclusions
In vivo 8-week tracing of dual-labelled MSCs can be achieved by MRI. Intracoronary
transplantation of dual-labelled MSCs can increase cardiac function and reduce the
size of MI in a swine model.
Résumé
Introduction
Notre objectif était de tracer et d'évaluer les transplantations intracoronariennes
de cellules souches mésenchymateuses (CSM) marquées par l'oxyde de fer superparamagnétique
(SPIO: superparamagnetic iron oxide) en utilisant l'imagerie par résonance magnétique
(IRM) appliquée à un modèle porcin d'infarctus du myocarde (IM).
Méthodes
Les CSM ont été transfectées par un vecteur lentiviral transportant le gène codant
pour la protéine verte fluorescente (GFP: green fluorescent protein) et marqué in vitro au SPIO. Deux (2) semaines après l'IM, le porc a été choisi de façon aléatoire pour
une transplantation intracoronarienne de CSM doublement marquées (n = 10), CSM-GFP
(n = 10) et de solution saline (n = 5). L'examen par IRM a été fait par un dispositif
de balayage clinique 1,5-T à 24 heures, trois (3) semaines et huit (8) semaines après
la transplantation de cellules. Les changements d'intensité du signal, la fonction
cardiaque et la taille de l'IM ont été mesurés au moyen de l'IRM. La corrélation entre
les découvertes par l'IRM et les découvertes histomorphologiques ont aussi été examinée.
Résultats
Les CSM ont pu être marquées de manière efficace et sécuritaire au SPIO et à la GFP,
et la multipotentialité n'a pas été perturbée, spécialement pour la différenciation
de la cellule ressemblant aux cardiomyocytes. L'intensité du signal sur l'image pondérée
en T2* a substantiellement diminué dans la cloison interventriculaire 24 heures après
l'injection de CSM. L'intensité des signaux hypo-intenses a semblé augmenter dans
les données les plus tardives. Les CSM ainsi que les CSM-GFP doublement marquées pourraient
remarquablement réduire la taille de l'IM et améliorer la fonction cardiaque. Les
données histologiques ont révélé que les cellules qui avaient obtenu une coloration
positive au bleu de Prusse ont été trouvées principalement dans la zone marginale,
laquelle a aussi montré une fluorescence verte.
Conclusion
Le tracé à huit (8) semaines in vivo des CSM doublement marquées peut être atteint par l'IRM. La transplantation intracoronarienne
de CSM doublement marquées peut augmenter la fonction cardiaque et réduire la taille
de l'IM à un modèle porcin.
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Article info
Publication history
Published online: October 24, 2011
Accepted:
July 19,
2011
Received:
March 25,
2011
Footnotes
See page 824 for disclosure information.
Identification
Copyright
© 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
