与总单核细胞相比，CD34阳性细胞在心肌梗死后治疗性新生血管形成方面表现出更高的效能和安全性。
CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells.
作者信息
Kawamoto Atsuhiko, Iwasaki Hiroto, Kusano Kengo, Murayama Toshinori, Oyamada Akira, Silver Marcy, Hulbert Christine, Gavin Mary, Hanley Allison, Ma Hong, Kearney Marianne, Zak Victor, Asahara Takayuki, Losordo Douglas W
机构信息
Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
出版信息
Circulation. 2006 Nov 14;114(20):2163-9. doi: 10.1161/CIRCULATIONAHA.106.644518. Epub 2006 Oct 30.
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), 5x10(5) CD34+ cells/kg, 5x10(5) tMNCs/kg (low-dose MNCs [loMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5x10(5) 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 mm2) than in the PBS, loMNC, and hiMNC groups (384.7+/-11.0, 372.5+/-14.1, and 497.5+/-24.0 per 1 mm2) (P<0.01). Percent fibrosis area on day 28 was less in the CD34(+) cell group (15.6+/-0.9%) than in the PBS, loMNC, 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, loMNC, 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, loMNC, 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.
背景
我们比较了纯化的动员人CD34+细胞与动员的总单核细胞（tMNCs）对心肌梗死后（MI）心肌组织完整性和功能的保存/恢复的治疗潜力。
方法与结果
在给予健康志愿者粒细胞集落刺激因子5天后，通过磁性细胞分选从外周血tMNCs中纯化CD34+细胞。在无胸腺裸鼠诱导MI 10分钟后，将磷酸盐缓冲盐水（PBS）、5×10⁵ CD34+细胞/kg、5×10⁵ tMNCs/kg（低剂量MNCs [loMNCs]）或含有5×10⁵ CD34+细胞/kg的更高剂量tMNCs（hiMNCs）心肌内注射。苏木精和伊红染色显示，与PBS和CD34+细胞组相比，hiMNC组在第3天中度至重度出血性MI更常见。对人特异性CD45进行免疫染色显示，hiMNC组缺血心肌中移植细胞来源的造血/炎症细胞分布丰富。第28天时，CD34+细胞组的毛细血管密度（每1平方毫米721.1±19.9个）显著高于PBS、loMNC和hiMNC组（每1平方毫米分别为384.7±11.0、372.5±14.1和497.5±24.0个）（P<0.01）。第28天时，CD34⁺细胞组的纤维化面积百分比（15.6±0.9%）低于PBS、loMNC和hiMNC组（分别为26.3±1.2%、27.5±1.8%和22.2±1.8%）（P<0.05）。第28天时，CD34+细胞组的超声心动图缩短分数（30.3±0.9%）显著高于PBS、loMNC和hiMNC组（分别为22.7±1.5%、23.4±1.1%和24.9±1.7%；P<0.05）。CD34+细胞组的超声心动图区域壁运动评分（21.8±0.5）比PBS、loMNC和hiMNC组（分别为25.4±0.4、24.9±0.4和24.1±0.6）保存更好（P<0.05）。
结论
与未分选的循环MNCs相比，CD34+细胞在心肌梗死后保存心肌完整性和功能方面表现出更高的疗效。
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