华通胶源间充质干细胞经冠状动脉移植治疗慢性缺血性心肌病的实验研究

目的探讨华通胶源间充质干细胞（WJMSCs）经冠状动脉移植治疗猪慢性缺血性心肌病（CIMP）的安全性和有效性。方法巴马小型猪29头,其中25头行左冠状动脉前降支球囊闭塞制作心肌梗死后CIMP模型,以超声心动图检查左室射血分数（LVEF）≤45%为CIMP成功标准,其余4头为假手术（Sham）组。造模成功17头,3头未成功,5头死亡,研究初始6头CIMP模型猪（3头成功造模＋3头造模未成功）先行WJMSCs经冠状动脉移植剂量选择安全性实验,依次以6×106、1×107、2×107剂量经冠状动脉移植,每剂量组小型猪2头,造模成功与未成功者各1头,以TIMI 3级为安全剂量。余14头CIMP模型猪被...

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Bibliographic Details
Published in解放军医学杂志 Vol. 40; no. 11; pp. 885 - 891
Main Author 张宁坤 陈宇 王志国 李俊风 王丽华 朱智明 王力 高连如
Format Journal Article
LanguageChinese
Published 2015
Subjects
冠状血管
华通氏胶
心肌缺血
间质干细胞移植
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ISSN0577-7402

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Summary:目的探讨华通胶源间充质干细胞（WJMSCs）经冠状动脉移植治疗猪慢性缺血性心肌病（CIMP）的安全性和有效性。方法巴马小型猪29头,其中25头行左冠状动脉前降支球囊闭塞制作心肌梗死后CIMP模型,以超声心动图检查左室射血分数（LVEF）≤45%为CIMP成功标准,其余4头为假手术（Sham）组。造模成功17头,3头未成功,5头死亡,研究初始6头CIMP模型猪（3头成功造模＋3头造模未成功）先行WJMSCs经冠状动脉移植剂量选择安全性实验,依次以6×106、1×107、2×107剂量经冠状动脉移植,每剂量组小型猪2头,造模成功与未成功者各1头,以TIMI 3级为安全剂量。余14头CIMP模型猪被随机分为WJMSCs移植组和对照组（n=7）,分别经冠状动脉移植WJMSCs（2×107）,或注入生理盐水。在WJMSCs移植8周后,对两组模型猪进行超声心动图、病理组织学、免疫荧光学检测。结果 CIMP小型猪在WJMSCs移植8周后,LVEF较移植前增高11.6%（P〈0.01）,左室收缩末容积减少4.1ml（P〈0.05）,而对照组心室功能进一步恶化（LVEF从42.8%下降为35.9%,P〈0.01）,左室进一步扩张（左室舒张末容积从42.8±1.2ml进展为46.7±1.3ml,P〈0.05）。病理组织学检查显示WJMSCs移植组梗死区心室壁厚度明显增厚,梗死边缘区血管密度明显增加。免疫荧光检测可见带有Myc标志的WJMSCs在梗死心肌内存活,且与心肌肌钙蛋白T、α-actin和Connexin-43共表达。结论经冠状动脉移植WJMSCs治疗猪慢性CIMP是安全、有效的。
Bibliography:11-1056/R
Wharton jelly; mesenchymal stem cell transplantation; coronary vessels; myocardial ischemia
Objective To investigate the safety and efficacy of transplantation of allogeneic Wharton＇s jelly-derived mesenchymal stem cells（WJMSCs） in a porcine model of chronic ischemia cardiomyopathy. Methods Cardiomyopathy models（CIMP） were reproduced in 25 minipigs out of 29 by left anterior descending coronary artery balloon occlusion, and the 4 remains served as sham group. The left ventricular ejection fraction（LVEF） was detected by echocardiography, and the value ≤45% was defined as successful modeling. Of that 25 minipigs, 5 died, 3 failed of modeling and 17 remains were successfully modelled. The dose safety experiment of WJMSCs transplantation was firstly performed in 3 successful models and 3 failed models. Three doses were tested in turn at 6×106, 1×107 and 2×107 with 1 successful and 1 failed model for each dose, and TIMI 3 was considered safety dosage. The remainder 14 CIMP models were randomly assigned to
ISSN:0577-7402