应用干细胞工程化递送平台于急性梗死心肌后肌细胞凋亡的无创成像。
Noninvasive imaging of myocyte apoptosis following application of a stem cell-engineered delivery platform to acutely infarcted myocardium.
机构信息
Department of Biomedical Engineering, Columbia University Medical Center, New York, New York, USA.
出版信息
J Nucl Med. 2013 Jun;54(6):977-83. doi: 10.2967/jnumed.112.112979. Epub 2013 Apr 24.
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.
背景
间充质干细胞（MSCs）的心脏保护作用包括减少心肌细胞凋亡，这种作用可以通过预处理和包封在纤维蛋白支架中得到增强。本研究旨在通过在急性心肌梗死大鼠模型中检测条件 MSC 贴片移植的心脏保护作用来验证假说。
方法
模拟纤维蛋白贴片移植到暴露于缺氧的大鼠心室肌细胞上的细胞培养实验表明，条件细胞具有减少细胞凋亡的作用。23 只裸鼠成功进行了左前降支冠状动脉闭塞，并分为 3 组：转化生长因子β 1 条件化人 MSC 负载贴片（CP）、梗死组无贴片（NP）和贴片组（PO）。心肌梗死后 24 小时，所有大鼠均注射（99m）Tc-肼基烟酰胺（（99m）Tc-HYNIC） annexin V 和（201）Tl，并进行双同位素 SPECT/CT 成像。6 只大鼠用于组织学和计数。其余大鼠（n=17；1 只大鼠被淘汰）于第 7 天注射和成像；其中，3 只大鼠用于组织学和计数，其余 13 只大鼠存活至第 21 天，此时进行组织学检查。第 3 组中在第 7 天进行成像的大鼠数量分别为 CP 组 7 只，NP 组 5 只，PO 组 5 只。从第 1 天和第 7 天的扫描中定量评估灌注心肌、梗死面积和（99m）Tc-HYNIC annexin V 摄取。（99m）Tc-HYNIC annexin V 摄取与定量半胱氨酸天冬氨酸蛋白酶染色相关，第 21 天定量纤维化的梗死面积。
结果
CP 组、NP 组和 PO 组第 1 天至第 7 天（99m）Tc-HYNIC annexin V 摄取率（×10（-4））分别下降 1.04±0.28、0.44±0.17 和 0.34±0.27（NP 与 CP 相比，P=0.003；PO 与 CP 相比，P=0.005；NP 与 CP 相比，P=0.5）。第 1 天至第 7 天之间，CP 组、NP 组和 PO 组的缺陷大小百分比变化分别为-8.83±4.40、+1.00±2.24 和-0.50±4.20（NP 与 CP 相比，P=0.003；PO 与 CP 相比，P=0.005；NP 与 CP 相比，P=0.5）。（99m）Tc-HYNIC annexin V 摄取率通过扫描与半胱氨酸天冬氨酸蛋白酶染色相关（r=0.931，P=0.002）。
结论
转化生长因子β 1 条件化人 MSC 负载贴片可减少急性梗死时的心肌细胞凋亡，通过（99m）Tc-HYNIC annexin V 体内成像可以检测到这种作用。
Zotero 插件