Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction.
Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction.
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冠状动脉内移植来自人类脂肪组织来源的多谱系祖细胞的成肌细胞样细胞可改善慢性心肌梗塞猪模型的左心室功能障碍和存活率。
DOI：
10.1016/j.bbrc.2012.08.004
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Matsuyama A.
中科院分区：
文献类型：
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作者：
Okura H;Saga A;Soeda M;Miyagawa S;Sawa Y;Daimon T;Ichinose A;Matsuyama A.
从人脂肪组织来源的多系祖细胞移植人成心肌细胞样细胞（hCLC）改善心肌梗死大鼠的左心室功能和存活率。在此，我们研究了人CLC冠状动脉内移植在慢性心力衰竭猪模型中的作用。24只猪行第一对角分支球囊闭塞后再灌注，1周后行第二次左冠状动脉升支球囊闭塞后再灌注。在第二次闭塞/再灌注后4周，对18只存活的患有严重慢性MI（超声心动图显示射血分数<35%）的动物中的17只进行免疫抑制，然后随机分配接受hCLC hADMPC的冠状动脉内移植或安慰剂乳酸林格氏溶液与肝素。冠状动脉内移植后，DiI染色的hCLC分布到瘢痕心肌环境中。移植后第4和8周的超声心动图显示移植组心脏功能得到了挽救和维持，而对照组则没有，表明hCLC冠状动脉内移植可恢复心肌功能。在移植后8周，8只hCLC移植动物中有7只仍然存活，而5只对照动物中只有1只存活（p=0.0147）。移植后12周的组织学研究表明，预DiI染色的hCLC植入瘢痕心肌中，并表达人特异性α-心脏肌动蛋白。人α心脏肌动蛋白阳性细胞也表达心脏核因子; nkx 2.5和加塔-4。我们的研究结果表明，冠状动脉内移植的hCLC是一个潜在的有效的治疗策略，为未来的心脏组织再生。
Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer’s solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p=0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.