Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium.
Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium.
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DOI：
10.1161/circresaha.116.304668
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发表时间：
2015-03-27
影响因子：
20.1
通讯作者：
Yang PC
中科院分区：
文献类型：
--
作者：
Kim PJ;Mahmoudi M;Ge X;Matsuura Y;Toma I;Metzler S;Kooreman NG;Ramunas J;Holbrook C;McConnell MV;Blau H;Harnish P;Rulifson E;Yang PC
干细胞治疗的功能恢复机制仍然知之甚少。新型锰增强MRI和生物发光报告基因成像（BLI）分别用于随访心肌存活率和细胞植入。人胎盘来源的羊膜间充质干细胞（AMC）表现出独特的免疫调节和心前特性。在这项研究中，在鼠心肌损伤模型中检查了三种AMC衍生的亚群的恢复作用：1）ckit AMC（uAMC），2）ckit+ AMC（c+ AMC），和3）AMC衍生的iPSC（MiPSC）。使用多模态成像确定AMC衍生的亚群在鼠心肌损伤模型中的不同恢复作用。将SCID小鼠进行左前降支动脉结扎并分成4个治疗组：1）生理盐水对照（n=14），2）uAMC（n=10），3）c+ AMC（n=13）和4）MiPSC（n=11）。心脏MRI评估了心肌存活率和左心室（LV）功能，而BLI评估了四周内的干细胞植入。采用免疫组化标记和RT-PCR技术对心肌组织进行标记。uAMC和c+AMC处理的小鼠表现出短暂的LV功能改善。然而，在整个四周期间，与所有其他组相比，MiPSC表现出显著更大的LV功能增加。LV功能改善与心肌存活率增加和持续干细胞植入相关。经MiPSC处理的动物缺乏从头心脏分化的任何证据。在MiPSC中观察到的功能恢复的特征在于增加的心肌活力和持续的植入，而没有从头心脏分化，表明损伤心肌的挽救。
The mechanism of functional restoration by stem cell therapy remains poorly understood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging (BLI) were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta-derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and pre-cardiac properties. In this study, the restorative effects of three AMC-derived sub-populations were examined in a murine myocardial injury model: 1) unselected AMCs (uAMCs), 2) ckit+AMCs (c+AMCs), and 3) AMC-derived iPSCs (MiPSCs). Determine the differential restorative effects of the AMC-derived sub-populations in the murine myocardial injury model using multi-modality imaging. SCID mice underwent left anterior descending artery ligation and were divided into 4 treatment arms: 1) normal saline control (n=14), 2) uAMCs (n=10), 3) c+AMCs (n=13), and 4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular (LV) function while BLI assessed stem cell engraftment over a four-week period. Immunohistological labeling and RT-PCR of the explanted myocardium were performed. The uAMC and c+AMC treated mice demonstrated transient LV functional improvement. However, the MiPSCs exhibited a significantly greater increase in LV function compared to all the other groups during the entire four-week period. LV functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSCs treated animals lacked any evidence of de novo cardiac differentiation. The functional restoration seen in MiPSCs was characterized by increased myocardial viability and sustained engraftment without de novo cardiac differentiation, indicating salvage of the injured myocardium.