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促红细胞生成素能否改善梗死心肌中骨骼肌成肌细胞的植入?

Can erythropoietin improve skeletal myoblast engraftment in infarcted myocardium?

作者信息

Chanséaume Sylvain, Azarnoush Kasra, Maurel Agnès, Bellamy Valérie, Peyrard Séverine, Bruneval Patrick, Hagège Albert A, Menasché Philippe

机构信息

INSERM U 633, Laboratoire d'Etude des Greffes et Prothèses Cardiaques, Hôpital Broussais; Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France.

出版信息

Interact Cardiovasc Thorac Surg. 2007 Jun;6(3):293-7. doi: 10.1510/icvts.2006.144014. Epub 2007 Mar 26.

DOI:10.1510/icvts.2006.144014
PMID:17669846
Abstract

The benefits of skeletal myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirty-five Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, skeletal myoblasts (5x10(6)) or skeletal myoblasts with EPO started the day before transplantation and continued for two weeks (500 U/kg three times a week). A fourth group was treated by EPO alone without injections. Function was assessed by 2D echocardiography before transplantation and one month thereafter. Compared with controls and hearts treated by EPO-alone, those transplanted with myoblasts yielded a significantly better recovery of LV ejection fraction, irrespective of whether they had received EPO or not. Neither the area of myoblast engraftment, nor angiogenesis differed between the myoblast-alone and the myoblast+EPO groups. Apoptosis was hardly detectable and, therefore, unaffected by EPO therapy. In this model, EPO failed to improve myoblast engraftment and postinfarction LV function. These negative findings justify to pursue the search for alternate cell survival-enhancing strategies.

摘要

骨骼肌成肌细胞移植的益处受到早期细胞死亡率高的限制,而早期细胞死亡部分源于缺血。因此,我们评估了通过额外使用血管生成细胞因子促红细胞生成素(EPO)是否可以提高移植物的存活率。35只Lewis大鼠接受冠状动脉结扎,两周后,随机分组接受瘢痕内注射对照培养基、骨骼肌成肌细胞(5×10⁶)或在移植前一天开始并持续两周(每周三次,每次500 U/kg)使用EPO的骨骼肌成肌细胞。第四组仅接受EPO治疗而不进行注射。在移植前及移植后1个月通过二维超声心动图评估心功能。与对照组和仅接受EPO治疗的心脏相比,移植了成肌细胞的心脏左室射血分数恢复明显更好,无论是否接受了EPO治疗。单独成肌细胞组和成肌细胞+EPO组之间,成肌细胞植入面积和血管生成均无差异。几乎检测不到凋亡,因此不受EPO治疗的影响。在该模型中,EPO未能改善成肌细胞植入和梗死后左室功能。这些阴性结果表明有必要继续寻找其他增强细胞存活的策略。

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引用本文的文献

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Skeletal myoblasts for cardiac repair.骨骼肌成肌细胞用于心脏修复。
Regen Med. 2010 Nov;5(6):919-32. doi: 10.2217/rme.10.65.
2
Stem cells and cardiac repair: a critical analysis.干细胞与心脏修复:批判性分析。
J Cardiovasc Transl Res. 2008 Mar;1(1):41-54. doi: 10.1007/s12265-007-9008-7. Epub 2008 Jan 31.
3
Blunting effect of hypoxia on the proliferation and differentiation of human primary and rat L6 myoblasts is not counteracted by Epo.缺氧对人原代和大鼠 L6 成肌细胞增殖和分化的抑制作用不能被 Epo 拮抗。
Cell Prolif. 2010 Feb;43(1):1-8. doi: 10.1111/j.1365-2184.2009.00648.x.
4
Transplantation of genetically engineered cardiac fibroblasts producing recombinant human erythropoietin to repair the infarcted myocardium.移植产生重组人促红细胞生成素的基因工程心脏成纤维细胞以修复梗死心肌。
Fibrogenesis Tissue Repair. 2008 Nov 3;1(1):7. doi: 10.1186/1755-1536-1-7.
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Systems approaches to preventing transplanted cell death in cardiac repair.预防心脏修复中移植细胞死亡的系统方法。
J Mol Cell Cardiol. 2008 Oct;45(4):567-81. doi: 10.1016/j.yjmcc.2008.03.009. Epub 2008 Mar 19.