Cedar Sinai Heart Institute, Los Angeles, CA, USA.
J Cardiovasc Pharmacol Ther. 2010 Dec;15(4):338-43. doi: 10.1177/1074248410376382.
Clinical trials of stem cell therapy in cardiology are based upon a reasonably solid foundation in animal laboratory research. The most widely used cell source in clinical trials has been the patient's own reconstituted bone marrow cell (BMC) aspirate. Cell sources in human bone marrow include hematopoietic stem cells, mesenchymal progenitor cells, and other cell types with many desirable characteristics. In vitro, they can be induced to become typical sarcomeres with centrally positioned nuclei and abundant mitochondria and to express atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and contractile proteins including myosin heavy chain, myosin light chain, and alpha actin. Intracoronary BMC infusion significantly decreases infarct size, increases myocardial perfusion, and improves regional and global cardiac function. Meta-analyses of clinical trials of intracoronary autologous BMC infusion following acute myocardial infarction (MI) report that the mean absolute increase in ejection fraction (EF) is approximately 3% to 4%. This modest improvement in function appears to persist for 1 year. Some trials have shown that clinical events are reduced at 12 months, but others have reported no long-term clinical benefit, and the only 5-year follow-up suggests persistent benefit with decreased mortality, but also little evidence of significant myocardial regeneration in humans. These results have led to efforts to identify better cell sources and to create more conducive myocardial environment for cell proliferation. Among the cell types are skeletal myoblasts, cardiac stem cells, and induced pluripotent stem cells. Environmental modifiers are designed to increase cell survival, persistence, and proliferation.
在心脏病学中，干细胞疗法的临床试验是基于动物实验室研究的合理基础。临床试验中最广泛使用的细胞来源是患者自身重建的骨髓细胞（BMC）抽吸物。人类骨髓中的细胞来源包括造血干细胞、间充质祖细胞和其他具有许多理想特征的细胞类型。在体外，它们可以被诱导成为具有中心定位核、丰富的线粒体并表达心房利钠肽（ANP）、脑利钠肽（BNP）和收缩蛋白的典型肌节，包括肌球蛋白重链、肌球蛋白轻链和α肌动蛋白。冠状动脉内 BMC 输注可显著减少梗塞面积、增加心肌灌注并改善局部和整体心脏功能。急性心肌梗死（MI）后冠状动脉内自体 BMC 输注临床试验的荟萃分析报告，射血分数（EF）的平均绝对增加约为 3%至 4%。这种功能的适度改善似乎持续 1 年。一些试验表明 12 个月时临床事件减少，但其他试验没有报告长期临床益处，唯一的 5 年随访表明死亡率持续降低，但也没有人类心肌再生的明显证据。这些结果导致人们努力寻找更好的细胞来源，并为细胞增殖创造更有利的心肌环境。这些细胞类型包括骨骼肌成肌细胞、心脏干细胞和诱导多能干细胞。环境修饰剂旨在增加细胞的存活率、持久性和增殖性。
