Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells
Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells
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DOI：
10.1161/circulationaha.109.849588
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发表时间：
2009-12-22
期刊：
影响因子：
37.8
通讯作者：
Barbash, Israel M.
中科院分区：
文献类型：
--
作者：
Itzhaki-Alfia, Ayelet;Leor, Jonathan;Barbash, Israel M.
人类心脏祖细胞（hCPCs）的鉴定和分离为心肌再生和修复提供了新的途径。尽管如此，人类心脏祖细胞的最佳来源以及患者特征对其数量的影响仍不清楚。使用一种新的方法分离人心脏祖细胞，我们的目标是确定最佳来源以及它们的数量和患者特征之间的关联。方法和结果-我们开发了一种新的分离方法，（7 x 10（6）+/- 6.53 x 10（5）/g），来自心脏手术或肌内膜活检期间获得的各种组织样本（来自94名23至80岁患者的113份样本）。分离的心肌细胞在干细胞扩增培养基中生长。根据荧光激活细胞分选分析，来自右心房的培养细胞产生更高量的c-kit（+）（24 +/- 2.5%）和培养物中的Islet-1（+）细胞（7%）（第1、2和3代的平均值）比来自左心房的培养细胞更高（7.3 ± 3.5%），右心室（4.1 ± 1.6%）和左心室（9.7 ± 3%; P = 0.001）。多因素分析显示，右心房作为细胞来源和女性与c-kit（+）细胞数量较高相关。c-kit（+）和Islet-1表达无重叠。体外成骨细胞、脂肪细胞和成肌细胞的分化实验表明，分离的人心脏祖细胞是多能的。最后，将细胞移植到大鼠的梗死心肌中并生成心肌graft.Conclusion-Our结果表明，右心房是c-kit（+）和Islet-1祖细胞的最佳来源，女性产生的c-kit（+）细胞的百分比较高。（循环。2009;120：2559-2566）。
Background-The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics.Methods and Results-We developed a novel isolation method that produced viable cells (7 x 10(6) +/- 6.53 x 10(5)/g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit(+) (24 +/- 2.5%) and Islet-1(+) cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3 +/- 3.5%), right ventricle (4.1 +/- 1.6%), and left ventricle (9.7 +/- 3%; P = 0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit(+) cells. There was no overlap between c-kit(+) and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts.Conclusion-Our results show that the right atrium is the best source for c-kit(+) and Islet-1 progenitors, with higher percentages of c-kit(+) cells being produced by women. (Circulation. 2009;120:2559-2566.)