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人脐带血来源的CD133+细胞增强梗死心肌的功能和修复。

Human umbilical cord blood-derived CD133+ cells enhance function and repair of the infarcted myocardium.

作者信息

Leor Jonathan, Guetta Esther, Feinberg Micha S, Galski Hanan, Bar Iris, Holbova Radka, Miller Liron, Zarin Parvin, Castel David, Barbash Israel M, Nagler Arnon

机构信息

Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel.

出版信息

Stem Cells. 2006 Mar;24(3):772-80. doi: 10.1634/stemcells.2005-0212. Epub 2005 Sep 29.

Abstract

The use of adult stem cells for myocardial tissue repair might be limited in elderly and sick people because their cells are depleted and exhausted. The present study was conducted to explore the potential of human umbilical cord blood (UCB) CD133+ progenitor cells for myocardial tissue repair in a model of extensive myocardial infarction (MI). CD133+ progenitor cells were isolated from newborn UCB. Cells (1.2-2 x 10(6)) or saline (control) was infused intravenously 7 days after permanent coronary artery ligation in athymic nude rats. Left ventricular (LV) function was assessed before and 1 month after infusion by echocardiography. Tracking of human cells was performed by fluorescent in situ hybridization for human X and Y chromosomes or by immunostaining for HLA-DR or HLA-ABC. One month after delivery, LV fractional shortening improved by 42 +/- 17% in cell-treated hearts and decreased by 39 +/- 10% in controls (p = .001). Anterior wall thickness decreased significantly in controls but not in treated hearts. Microscopic examination revealed that the UCB cells were able to migrate, colonize, and survive in the infarcted myocardium. Human cells were identified near vessel walls and LV cavity and were occasionally incorporated into endothelial cells in six of nine cell-treated animals but not in controls. Scar tissue from cell-treated animals was significantly populated with autologous myofibroblasts as indicated by colocalization of HLA-DR and alpha-smooth muscle actin staining. In conclusion, the present work suggests that, after MI, intravenous delivery of human UCB-derived CD133+ cells can produce functional recovery by preventing scar thinning and LV systolic dilatation.

摘要

由于老年人和病人的细胞已耗竭,使用成体干细胞进行心肌组织修复可能会受到限制。本研究旨在探讨人脐带血(UCB)CD133+祖细胞在广泛心肌梗死(MI)模型中对心肌组织修复的潜力。从新生儿脐带血中分离出CD133+祖细胞。在无胸腺裸鼠永久性冠状动脉结扎7天后,静脉注射细胞(1.2 - 2×10⁶)或生理盐水(对照)。在注射前和注射后1个月通过超声心动图评估左心室(LV)功能。通过对人X和Y染色体进行荧光原位杂交或对HLA - DR或HLA - ABC进行免疫染色来追踪人细胞。注射后1个月,细胞治疗组心脏的左心室缩短分数提高了42±17%,而对照组降低了39±10%(p = 0.001)。对照组前壁厚度显著降低,而细胞治疗组心脏则没有。显微镜检查显示,脐带血细胞能够在梗死心肌中迁移、定植并存活。在9只细胞治疗动物中的6只动物的血管壁和左心室腔附近发现了人细胞,这些细胞偶尔会整合到内皮细胞中,而对照组则未发现。如HLA - DR和α - 平滑肌肌动蛋白染色共定位所示,细胞治疗动物的瘢痕组织中有大量自体肌成纤维细胞。总之,目前的研究表明,心肌梗死后静脉注射人脐带血来源的CD133+细胞可通过防止瘢痕变薄和左心室收缩期扩张实现功能恢复。

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