Smith Rachel Ruckdeschel, Barile Lucio, Cho Hee Cheol, Leppo Michelle K, Hare Joshua M, Messina Elisa, Giacomello Alessandro, Abraham M Roselle, Marbán Eduardo
Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
Circulation. 2007 Feb 20;115(7):896-908. doi: 10.1161/CIRCULATIONAHA.106.655209. Epub 2007 Feb 5.
Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement.
Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group.
A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients.
对心脏驻留干细胞进行体外扩增，然后将其输送至心脏，可能有助于心脏再生和功能改善。
经皮心内膜活检标本在原代培养中形成了称为心球的多细胞簇，将这些心球接种后可产生心球衍生细胞（CDC）。对来自人类活检标本和类似猪样本的CDC进行体外检测，以寻找心脏发生分化的生物物理和细胞化学证据。此外，将人类CDC注射到免疫缺陷小鼠急性心肌梗死的边缘区。70例患者中的69例活检标本产生了形成心球的细胞。心球和CDC在处理的每个阶段都表达干细胞的抗原特征，以及对心脏收缩和电功能至关重要的蛋白质。与新生大鼠心室肌细胞共培养的人类和猪CDC表现出肌细胞特有的生物物理特征，包括与相邻肌细胞同步的钙瞬变。注射到心肌梗死边缘区的人类CDC能够植入并迁移到梗死区。20天后，梗死区内存活心肌的百分比在CDC治疗组中高于成纤维细胞治疗的对照组；同样，CDC治疗组的左心室射血分数更高。
本文介绍了一种从心内膜活检标本中分离成人干细胞的方法。CDC在体外具有心脏发生能力；它们在小鼠梗死模型中促进心脏再生并改善心脏功能，这为在患者中进一步开发治疗应用提供了动力。
