Noninvasive imaging of myocyte apoptosis following application of a stem cell-engineered delivery platform to acutely infarcted myocardium.

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 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 (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 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 (99m)Tc-HYNIC annexin V.

• Authors: Amandine F G Godier-Furnémont, Yared Tekabe, Maria Kollaros, George Eng, Alfredo Morales, Gordana Vunjak-Novakovic, Lynne L Johnson
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 54 Issue 6 Pg. 977-83 (Jun 2013) ISSN: 1535-5667 [Electronic] United States
• PMID: 23616583 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Annexin A5
• Organotechnetium Compounds
• technetium Tc 99m annexin V

Topics

• Acute Disease
• Animals
• Annexin A5
• Apoptosis
• Heart Ventricles (diagnostic imaging, pathology)
• Humans
• Ischemic Preconditioning, Myocardial
• Male
• Mesenchymal Stem Cells (cytology)
• Multimodal Imaging
• Myocardial Infarction (diagnostic imaging, pathology, therapy)
• Myocytes, Cardiac (pathology)
• Organ Size
• Organotechnetium Compounds
• Positron-Emission Tomography
• Rats
• Rats, Nude
• Tissue Engineering (methods)
• Tomography, X-Ray Computed