Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
Circulation. 2011 Jan 4;123(1):62-9. doi: 10.1161/CIRCULATIONAHA.108.832469. Epub 2010 Dec 20.
Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions.
Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 μm identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, n=4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, n=13; and healed MI implantation at 2 weeks, n=12). Assessment included echocardiography, magnetic resonance imaging, hemodynamics, triphenyltetrazolium chloride staining, and histological and molecular analyses. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared with controls had improved perfusion by magnetic resonance imaging (1.2±0.01 versus 0.86±0.05; P<0.01), decreased MI size (magnetic resonance imaging: left ventricle, 2.2±0.5% versus 5.4±1.5%, P=0.04; triphenyltetrazolium chloride: anterior wall, 10.3±4.6% versus 28.9±5.8%, P<0.03), and improved contractility (dP/dt, 1235±215 versus 817±817; P<0.05). In the healed MI cohort, treated animals had less decline in ejection fraction between 2 and 4 week assessment (-3±4% versus -13±-4%; P<0.05), less decline in ±dP/dt, and smaller MI (triphenyltetrazolium chloride, 21±11% versus 3±8%; P=0.006) than control animals. Infarcts in the treated animals contained more mdr-1(+) cells and fewer c-kit(+) cells with a trend for decreased expression of matrix metalloproteinase-2 and increased expression of tissue inhibitor of metalloproteinase-2.
Autologous cardiomyotissue implanted in an MI area remains viable, exhibits electromechanical coupling, decreases infarct size, and improves left ventricular function.
心肌梗死（MI）的细胞治疗可能受到细胞存活率低和缺乏转分化的限制。我们报告了一种将保存的心肌区域的整个自体心肌组织植入梗死区域的新技术。
使用 14 只大鼠优化心肌组织大小，用腹膜壁植入（300μm 被确定为最佳大小）。使用 39 只猪研究左前降支球囊闭塞诱导的 MI 中的心肌组织植入（10 只动物死亡；雄性到雌性的移植，用于原位杂交追踪 Y 染色体，n=4[2 个供体和 2 个 MI 动物]；急性 MI 植入队列在 1 小时，n=13；愈合 MI 植入在 2 周，n=12）。评估包括超声心动图、磁共振成像、血流动力学、三苯基四氮唑氯化物染色以及组织学和分子分析。追踪研究表明，具有供体细胞的植入物具有活力，这些细胞散布在相邻的心肌中，具有间隙连接和桥粒。在急性 MI 组中，与对照组相比，治疗动物的磁共振成像灌注得到改善（1.2±0.01 与 0.86±0.05；P<0.01），MI 面积减小（磁共振成像：左心室，2.2±0.5%与 5.4±1.5%，P=0.04；三苯基四氮唑氯化物：前壁，10.3±4.6%与 28.9±5.8%，P<0.03），收缩力提高（dP/dt，1235±215 与 817±817；P<0.05）。在愈合的 MI 组中，与对照组相比，治疗动物在 2 至 4 周评估时射血分数下降较少（-3±4%与-13±-4%；P<0.05），±dP/dt 下降较少，MI 较小（三苯基四氮唑氯化物，21±11%与 3±8%；P=0.006）。治疗动物的梗死区含有更多的 mdr-1（+）细胞和较少的 c-kit（+）细胞，基质金属蛋白酶-2 的表达降低，组织抑制剂金属蛋白酶-2 的表达增加。
植入 MI 区域的自体心肌组织仍然具有活力，表现出机电耦合，减小梗死面积，并改善左心室功能。
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