Noninvasive Imaging of Myocyte Apoptosis Following Application of a Stem Cell–Engineered Delivery Platform to Acutely Infarcted Myocardium

Journal of Nuclear Medicine

Amandine F.G. Godier-Furnémont¹  Yared Tekabe¹  Alfredo Morales¹  George Eng¹  Gordana Vunjak-Novakovic¹  Lynne L. Johnson¹  Maria Kollaros¹ 

关键词: apoptosis;    myocardial infarction;    stem cells;    radionuclides;    engineered cardiac tissue;   

DOI  :  10.2967/jnumed.112.112979

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 β1–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 99mTc-hydrazinonicotinamide (99mTc-HYNIC) annexin V and 201Tl 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 99mTc-HYNIC annexin V uptake were quantified from the scans from days 1 and 7. 99mTc-HYNIC annexin V uptake was correlated with quantitative caspase staining, and infarct size as percentage fibrosis was quantified at day 21. Results: 99mTc-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). 99mTc-HYNIC annexin V uptake as percentage left ventricle by scanning correlated with caspase staining (r = 0.931, P = 0.002). Conclusion: Transforming growth factor β1–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 99mTc-HYNIC annexin V.

【 授权许可】

Unknown