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在小鼠模型中通过心外膜沉积骨髓细胞包被的肌肉贴片修复心肌梗死

Repair of myocardial infarction by epicardial deposition of bone-marrow-cell-coated muscle patch in a murine model.

作者信息

Barandon Laurent, Couffinhal Thierry, Dufourcq Pascale, Alzieu Philippe, Daret Danièle, Deville Claude, Duplàa Cécile

机构信息

Department of Cardiovascular Surgery and Cardiology, Haut-Lévêque Hospital, Pessac, France.

出版信息

Ann Thorac Surg. 2004 Oct;78(4):1409-17. doi: 10.1016/j.athoracsur.2003.12.078.

DOI:10.1016/j.athoracsur.2003.12.078
PMID:15464506
Abstract

BACKGROUND

Myocardial infarction results in irreversible myocyte loss. In a murine model, we tested the feasibility of a novel repair technique combining bone marrow cell (BMC) transplantation and cardiomyoplasty.

METHODS

Myocardial infarction was induced cryogenically in backcrossed ROSA 26 transgenic x C57BL/6J mice (n = 75). Thirty days later, surviving mice (n = 69) were randomized to sham treatment (rethoracotomy only; n = 11), patch only treatment (n = 29), or patch + BMC treatment (n = 29). Abdominal muscle patches were harvested from donor littermates not expressing the beta-galactosidase reporter gene and sutured on the epicardium directly above the infarct zone. Patch only-treated mice received uncoated patches. Patch + BMC-treated mice received patches coated with 5 x 10(6) beta-galactosidase-expressing BMCs embedded in a collagen-rich three-dimensional matrix.

RESULTS

Mortality rate was 52% after muscle patch implantation. Bone marrow cells were able to migrate from muscle patch into the infarct zone, as demonstrated by beta-galactosidase immunostaining, and ultimately constituted 8% of all cells in scar tissue (mean +/- standard deviation, 219 +/- 111/mm2). Angiogenesis and cell survival in the scar were improved by patch + BMC treatment. Left ventricular geometry and cardiac function were improved by patch treatment, with or without BMC, although the effects were stronger after patch + BMC treatment.

CONCLUSIONS

Epicardial deposition of a BMC-coated muscle patch is a promising approach to restoring cardiac function after myocardial infarction.

摘要

背景

心肌梗死会导致不可逆的心肌细胞丢失。在一个小鼠模型中,我们测试了一种将骨髓细胞(BMC)移植与心肌成形术相结合的新型修复技术的可行性。

方法

在回交的ROSA 26转基因xC57BL/6J小鼠(n = 75)中通过冷冻诱导心肌梗死。30天后,存活的小鼠(n = 69)被随机分为假手术治疗组(仅再次开胸;n = 11)、仅贴片治疗组(n = 29)或贴片+BMC治疗组(n = 29)。从不表达β-半乳糖苷酶报告基因的供体同窝小鼠中获取腹部肌肉贴片,并直接缝合在梗死区域上方的心外膜上。仅贴片治疗的小鼠接受未包被的贴片。贴片+BMC治疗的小鼠接受包被有5×10⁶个表达β-半乳糖苷酶的BMC的贴片,这些BMC嵌入富含胶原蛋白的三维基质中。

结果

肌肉贴片植入后的死亡率为52%。通过β-半乳糖苷酶免疫染色证明,骨髓细胞能够从肌肉贴片迁移到梗死区域,最终占瘢痕组织中所有细胞的8%(平均值±标准差,219±111/mm²)。贴片+BMC治疗改善了瘢痕中的血管生成和细胞存活。无论有无BMC,贴片治疗均改善了左心室几何形状和心脏功能,尽管贴片+BMC治疗后的效果更强。

结论

BMC包被的肌肉贴片的心外膜沉积是心肌梗死后恢复心脏功能的一种有前景的方法。

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