CXCR4转基因骨髓间充质干细胞治疗心肌梗死的实验性研究  

Experimental Study of Intravenously Injected CXCR4 Transduced Mesenchymal Stem Cell in Myocardial Infarction

作　　者：李飞[1] 何辉[1] 付志刚[2] 

机构地区：[1]解放军254医院超声室,天津300142 [2]解放军254医院体检中心,天津300142

出　　处：《华北国防医药》2008年第4期1-5,F0002,共6页Medical Journal of Beijing Military Region

基　　金：国家自然科学基金(30570471);新世纪优秀人才支持计划;天津市科技发展计划项目(05YFJZJC01601)

摘　　要：目的:探讨骨髓间充质干细胞(MSCs)及CXCR4转基因MSCs(CXCR4-MSCs)治疗心肌梗死(MI)的机制、效果及简单有效的移植方法。方法:将SD大鼠随机分为假手术组、生理盐水组、细胞治疗的MSCs组及CXCR4-MSCs组。生理盐水组及细胞治疗组左冠状动脉前降支结扎60min后再灌注。术后24h,细胞治疗组分别经尾静脉注射2.5×106个DiI标定的体外扩增的MSCs/CXCR4-MSCs。生理盐水组注射1mL生理盐水。分别于术后3d及30d检查移植细胞MI区归巢情况及在MI区生存及分化情况。测定MI区胶原含量、胶原Ⅰ/Ⅲ比率。用超声心动图评估MI30d后各组鼠左心室功能等。结果:CXCR4-MSCs治疗组移植细胞归巢至MI区数目是MSCs治疗组的2.5倍,体外迁移实验中CXCR4-MSCs治疗组细胞向基质细胞衍生因子-1(SDF-1)迁移数目是MSCs治疗组的3.8倍,超声心动图评估MI区室壁变薄及心功能下降均轻于MSCs治疗组,与大体组织形态学改变吻合。细胞治疗组胶原Ⅰ/Ⅲ比率比生理盐水组明显下降75%以上。结论:CXCR4-MSCs恢复了植入的MSCs向梗死心肌的靶向迁移能力,提高了静脉移植MSCs治疗MI的效果。Objective：To study the mechanism（s） and curative effect of mesenchymal stem cells（MSCs）with transgene CXCR4-MSCs and to find a simple and effective therapy for the patients with myocardial infarction （MI）. Methods： The female SD rats were divided into/as three groups for MI model（ including the MSCs,the CXCR4-MSCs,the saline controls）and the sham operation group randomly. All of the MI rat model＇s left anterior descending coronary（LAD） were ligated for 60 minutes ,followed by reperfusion. Sham-operated rats made a passing a suture around the LAD without ligation. 24 hours after MI,2.5 × 10^6 Dil-labeled MSCs or CXCR4-MSCs or lml saline was injected through the tail vein. 3 days and 30 days after cells injection,the number of cells homing and differentiation in MI area was examined and MI size was measured. The total collagen content and the ratio of collagen Ⅰ / Ⅲ, also all of the group rates left ventricular（LV） function were evaluated by echocardiography 30 days after transplantation. Results：A transwell migration assay：the number of CXCR4-MSCs migrating toward SDF-1 was 3.8 fold greater than the number of MSCs ,the number of CXCR4 homing in toward the MI region was significantly increased to 2.5 fold more than the MSCs did. The echocardiographic data in concord with the histomorphological appearance that thinning of the anterior wall was reduced and LV function improved significantly in CXCR4-MSCs group as compared to that of MSCs and saline groups. The collagen Ⅰ / Ⅲ ratio was lower in the CXCR4-MSC-and MSCs-treated rats by 〉 75% as compared to the saline-control group. Conclusion：CXCR4-MSCs can enhance the ability of MSCs migrating toward MI region and improve the curative effect of MI by intravenous transplantation of MSCs.

关 键 词：骨髓移植 间质干细胞移植 心肌梗死 CXCR4受体 

分 类 号：R457.7[医药卫生—治疗学] R654[医药卫生—临床医学]