CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells
CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells
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DOI：
10.1161/circulationaha.106.644518
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发表时间：
2006-11-14
期刊：
影响因子：
37.8
通讯作者：
Losordo, Douglas W.
中科院分区：
文献类型：
--
作者：
Kawamoto, Atsuhiko;Iwasaki, Hiroto;Losordo, Douglas W.
背景-我们比较了纯化的动员的人CD 34（+）细胞与动员的总单个核细胞（tMNCs）在心肌梗死（MI）后心肌组织完整性和功能的保存/恢复方面的治疗潜力。刺激因素在无胸腺裸大鼠中诱导MI后10分钟，将磷酸盐缓冲盐水（PBS）、5 x 10（5）CD 34（+）细胞/kg、5 x 10（5）tMNC/kg（低剂量MNC [1 oMNC]）或含有5 x 105 CD 34（+）细胞/kg的更高剂量tMNC（hiMNC）植入心肌内。苏木精和伊红染色显示，第3天hiMNC组中中度至重度出血性MI的发生率高于PBS和CD 34（+）细胞组。对人特异性CD 45的免疫染色显示，在hiMNC组的缺血心肌中，来源于移植细胞的造血/炎性细胞分布丰富。第28天，CD 34（+）细胞组的毛细血管密度（721.1 +/- 19.9/1 mm 2）显著高于PBS、1 oMNC和hiMNC组（384.7 +/- 11.0、372.5 +/- 14.1和497.5 +/- 24.0/1 mm 2）（P < 0.01）。第28天，CD 34（+）细胞组（15.6 +/- 0.9%）的纤维化面积百分比低于PBS、1 oMNC和hiMNC组（26.3 +/-1.2%、27.5 +/-1.8%和22.2 +/- 1.8%）（P < 0.05）。第28天，CD 34（+）细胞组（30.3 +/- 0.9%）的超声心动图短轴分数显著高于PBS、1 oMNC和hiMNC组（22.7 +/-1.5%、23.4 +/-1.1%和24.9 +/- 1.7%; P < 0.05）。CD 34（+）细胞组的超声心动图局部室壁运动评分保持较好（21.8 +/- 0.5）比PBS、1 oMNC和hiMNC组（25.4 ± 0.4，24.9 ± 0.4和24.1 ± 0.6;结论：CD 34（+）细胞在心肌梗死后对心肌完整性和功能的保护作用上级外周血单个核细胞。
Background - We compared the therapeutic potential of purified mobilized human CD34(+) cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI).Methods and Results - CD34(+) cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5 x 10(5) CD34(+) cells/kg, 5 x 10(5) tMNCs/kg (low-dose MNCs [1oMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5 x 105 CD34(+) cells/kg was transplanted intramyocardially 10 minutes after the induction of MI in athymic nude rats. Hematoxylin and eosin staining revealed that moderate to severe hemorrhagic MI on day 3 was more frequent in the hiMNC group than in the PBS and CD34(+) cell groups. Immunostaining for human-specific CD45 revealed abundant distribution of hematopoietic/inflammatory cells derived from transplanted cells in the ischemic myocardium of the hiMNC group. Capillary density on day 28 was significantly greater in the CD34(+) cell group (721.1 +/- 19.9 per 1 mm(2)) than in the PBS, 1oMNC, and hiMNC groups (384.7 +/- 11.0, 372.5 +/- 14.1, and 497.5 +/- 24.0 per 1 mm(2)) (P < 0.01). Percent fibrosis area on day 28 was less in the CD34(+) cell group (15.6 +/- 0.9%) than in the PBS, 1oMNC, and hiMNC groups (26.3 +/- 1.2%, 27.5 +/- 1.8%, and 22.2 +/- 1.8%) ( P < 0.05). Echocardiographic fractional shortening on day 28 was significantly higher in the CD34(+) cell group (30.3 +/- 0.9%) than in the PBS, 1oMNC, and hiMNC groups (22.7 +/- 1.5%, 23.4 +/- 1.1%, and 24.9 +/- 1.7%; P < 0.05). Echocardiographic regional wall motion score was better preserved in the CD34(+) cell group (21.8 +/- 0.5) than in the PBS, 1oMNC, and hiMNC groups (25.4 +/- 0.4, 24.9 +/- 0.4, and 24.1 +/- 0.6; P < 0.05).Conclusions - CD34(+) cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.