Zhou Yifu, Wang Suna, Yu Zuxi, Hoyt Robert F, Sachdev Vandana, Vincent Pamela, Arai Andrew E, Kwak Minjung, Burkett Sandra Sczerba, Horvath Keith A
Cellular Biology Section, Cardiothoracic Surgery Research Program, NHLBI, National Institutes of Health, 10 Center Drive, MSC 1550, Building 10, Room 2N246, Bethesda, MD 20892-1550, USA.
Biochem Biophys Res Commun. 2009 Dec 18;390(3):902-7. doi: 10.1016/j.bbrc.2009.10.074. Epub 2009 Oct 21.
Cell-based therapies have been employed with conflicting results. Whether direct injection of ex-vivo expanded autologous marrow stromal cells (MSCs) would improve the function of ischemic myocardium and enhance angiogenesis is not well defined. In a porcine model of chronic ischemia, MSCs were isolated and cultured for 4 weeks. Sixteen animals were random divided into two groups to receive either direct intramyocardial injection of autologous MSCs, or equal volumes and injections sites of saline. Cine MRI and epicardial echocardiography were performed just prior to the injections and again 6 weeks later at the time of sacrifice at which point tissue was also analyzed. Myocardial function as assessed by regional wall thickening (as measured by dobutamine stress echocardiograms) demonstrated a 40.9% improvement after cell treatment of the ischemic zone (p=0.016) whereas the saline treated animals only had a 3.7% change (p=0.82) compared to baseline. The left ventricular ejection fractions of MSC group showed 19.5% improvement from baseline 35.9+/-3.8% to 42.9+/-5.8% (p=0.049). Increased vascularity was found in the MSC group compared to controls (0.80+/-0.30 vs 0.50+/-0.19 capillary/myocyte ratio, p=0.018). Direct injection of autologous MSCs promotes angiogenesis and enhances the functional improvements following chronic myocardial ischemia. This suggests that the angiogenesis engendered by cell treatment may be physiologically meaningful by improving the contractility of ischemic myocardium.
基于细胞的疗法应用结果不一。直接注射体外扩增的自体骨髓基质细胞（MSC）是否能改善缺血心肌功能并促进血管生成，目前尚不明确。在一个慢性缺血的猪模型中，分离并培养MSC 4周。16只动物随机分为两组，分别接受自体MSC心肌内直接注射，或等量体积和注射部位的生理盐水注射。在注射前及6周后处死动物时分别进行电影磁共振成像（Cine MRI）和心外膜超声心动图检查，此时还对组织进行分析。通过局部室壁增厚评估的心肌功能（通过多巴酚丁胺负荷超声心动图测量）显示，缺血区细胞治疗后改善了40.9%（p = 0.016），而生理盐水治疗的动物与基线相比仅变化了3.7%（p = 0.82）。MSC组的左心室射血分数从基线的35.9±3.8%提高到42.9±5.8%，改善了19.5%（p = 0.049）。与对照组相比，MSC组血管增多（毛细血管/心肌细胞比例为0.80±0.30 vs 0.50±0.19，p = 0.018）。直接注射自体MSC可促进慢性心肌缺血后的血管生成并增强功能改善。这表明细胞治疗产生的血管生成可能通过改善缺血心肌的收缩性而具有生理意义。
