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我们自己的研究也发现自体骨髓间充质细胞移植对OMI患者也是安全有效的,22例陈旧性心肌梗死伴心功能不全患者随机分为对照组和移植组各11例,在常规药物治疗的基础上,经冠状动脉内注射自身骨髓间质干细胞或等量生理盐水。术后3个月和6个月,与对照组比较,细胞移植组BNP降低,6min步行试验距离增加,与自身术前比较差异亦具显著性。术后3个月,细胞移植组LVEF增加,与对照组和自身术前比较差异有显著性(0.40±0.03比0.37±0.09,0.35±0.05,P<0.05)。术后6月,细胞移植组左室舒张末容积缩小,与对照组和自身术前比较差异有显著性。双核素心肌显像提示移植组术后6个月灌流—代谢不匹配节段数增加,与对照组和自身术前比较差异具显著性(7.60±1.26比6.20±1.14,5.80±1.69,P<0.05)。围手术期及术后6个月随访中未见任何严重心律失常发生。对于原发性扩张型心肌病,MSCs移植虽然不改变LVEF,但能改善6min步行试验,降低BNP的增高,改善心功能不全。
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四、结 论
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目前提高MSCs存活的方法主要有转染促存活基因以及用细胞因子和其他物质处理MSCs等,取得一定的效果。但用病毒转染时有免疫原性及毒性作用,可能会限制在临床上的使用,所以需要寻找一种更安全有效的转染方法。另外转染的基因高表达也会带来一定的风险。而用细胞因子和其他物质处理MSCs仍处于体外细胞的研究阶段,其疗效还需要大量的体内动物实验以及大规模、多中心、双盲、对照临床研究来证实。ASTAMI(autologous stem cell transplantation in acute myocardial infarction)研究发现细胞移植前后 CK、CK-MB无明显改变。REPAIR-AMI研究发现随访4个月时细胞移植组LVEF增加更多,1年时临床事件(包括死亡、心肌梗死再发、血运重建)更少;细胞移植组和对照组均有2例死亡,对照组6例再发心肌梗死,血运重建更多(28
:19)。关于再狭窄,MAGIC Cell-3-DES试验已证实在药物涂层支架基础上干细胞治疗并不增加再狭窄。因此从目前的证据看,缺血性心脏病的干细胞治疗是安全有效并且切实可行的。未来应该进行更大样本(每组几百例)、更长时间(3~5年)的大规模随机对照多中心研究来进一步评价它的效果和风险。同时基础和临床研究应该齐头并进,明确哪种细胞能够真正有效改善心功能、细胞移植的效果能持续多久、如何安全有效地提高移植后MSCs存活率、重复移植是否带来更大的益处等。
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【思考题】
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1.细胞移植治疗充血性心力衰竭的可能机理如何?
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2.目前用于临床治疗充血性心力衰竭的移植细胞有哪些?有哪些证据支持?
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3.试述干细胞的特性及分类,并举例说明。
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参考文献
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