Noninvasive imaging of myocyte apoptosis following application of a stem cell-engineered delivery platform to acutely infarcted myocardium.
J Nucl Med
; 54(6): 977-83, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23616583
ABSTRACT
UNLABELLED The cardioprotective effects of mesenchymal stem cells (MSCs) include reducing myocyte apoptosis, and this effect can be enhanced by preconditioning and encapsulation in a fibrin scaffold. This study aimed to test the hypothesis that apoptosis imaging can detect the cardioprotective effects of a conditioned MSC patch grafted in a rat model of acute myocardial infarction. METHODS:
Cell culture experiments simulating engraftment of fibrin patches onto beating rat ventricular myocytes exposed to hypoxia showed an effect of conditioned cells to reduce apoptosis. Twenty-three nude rats underwent successful left anterior descending coronary artery occlusion and were divided into 3 groups transforming growth factor ß1-conditioned human MSC-laden patches (CP), infarct alone without patch (no patch [NP]), and patch alone (patch only [PO]). Twenty-four hours after myocardial infarction, all rats were injected with (99m)Tc-hydrazinonicotinamide ((99m)Tc-HYNIC) annexin V and (201)Tl and underwent dual-isotope SPECT/CT imaging. Six rats were sacrificed for histology and counting. The remaining rats (n = 17; 1 rat was eliminated) were injected and imaged on day 7; of those, 3 rats were sacrificed for histology and counting, and the remaining 13 rats survived to day 21, when they were sacrificed for histology. Numbers of rats imaged on day 7 in the 3 groups were 7 in the CP group, 5 in the NP, and 5 in the PO. Perfused myocardium, infarct size, and (99m)Tc-HYNIC annexin V uptake were quantified from the scans from days 1 and 7. (99m)Tc-HYNIC annexin V uptake was correlated with quantitative caspase staining, and infarct size as percentage fibrosis was quantified at day 21.RESULTS:
(99m)Tc-HYNIC annexin V uptake as percentage injected dose (×10(-4)) decreased between days 1 and 7 by 1.04 ± 0.28 in the CP group, 0.44 ± 0.17 in the NP group, and 0.34 ± 0.27 in the PO group (P = 0.003 for NP vs. CP, P = 0.005 for PO vs. CP, and P = 0.5 for NP vs. CP). The changes in defect size as percentage myocardium between days 1 and 7 were -8.83 ± 4.40 in the CP group, +1.00 ± 2.24 in the NP group, and -0.50 ± 4.20 in the PO group (P = 0.003 for NP vs. CP, P = 0.005 for PO vs. CP, and P = 0.50 for NP vs. PO). (99m)Tc-HYNIC annexin V uptake as percentage left ventricle by scanning correlated with caspase staining (r = 0.931, P = 0.002).CONCLUSION:
Transforming growth factor ß1-conditioned human MSC-laden patches reduce myocyte apoptosis in the setting of acute infarction, and this effect can be detected by in vivo imaging with (99m)Tc-HYNIC annexin V.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tomografia Computadorizada por Raios X
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Apoptose
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Engenharia Tecidual
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Miócitos Cardíacos
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Tomografia por Emissão de Pósitrons
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Células-Tronco Mesenquimais
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Imagem Multimodal
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Infarto do Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Nucl Med
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos