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[QICC2012]终末期心脏病的心脏再生治疗
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作者:徐标|花颖 编辑:国际循环网 时间:2012/8/10 16:36:07    加入收藏
 关键字:终末期心脏病 干细胞治疗 


  干细胞治疗在临床应用方面存在的问题
  现今,干细胞治疗仍遇到很多困难,首先是如何使更多的治疗细胞存活下来。有研究显示约90%的移植细胞在治疗的第一周内死亡,其最主要的原因是给药时大部分的细胞被循环带走而无法起作用。而在缺血性心肌病的猪模型中发现直接心肌内注射比冠脉内给药能更好地保留移植细胞[19],但它需通过开胸得以实现而在临床上受到限制,因此在未来我们可以开发侵袭性较小的导管介入技术来弥补这一不足。其次是异体移植细胞的问题,为避免免疫排斥反应,在开始的临床实验中多采用自体细胞,但自体细胞投入临床需要大量人力资源,且治疗效果存在个体差异。因此若可避免或减少免疫排除反应,异体移植细胞将比自体细胞更加适用于临床,现已发现骨髓间充质干细胞有免疫豁免能力,在修复损伤心肌、改善心功能方面有很大临床应用潜能[20]。最后是临床适用人群,在开始的研究中,干细胞治疗多用于初发心肌梗死,无左室功能不全的病人。事实上多项临床实验显示心肌梗死后心功能损伤程度越重[12],病人的获益越多,包括基础EF值的提高及终点事件的下降。由此可见干细胞治疗可能对心肌梗死程度较重的病人更为有益。
  除了干细胞治疗外,Ieda M等应用基因重编技术直接将心肌成纤维细胞转化为心肌细胞[21],成为再生医学领域的重大突破,此外基因治疗也成为心脏再生领域的一大亮点,如Kuhn[22] 等发现 NRG1/ErbB4 信号通路可以诱导成年心肌细胞的增殖和损伤修复。而在我们实验室Ding[23]等发现高表达整合素连接激酶(ILK)可改善心肌梗死后左室收缩功能, 逆转心肌重塑,并且其作用与心肌细胞增殖有关,而Gu等在扩张型心肌病的大鼠模型中也得到相似的结论。由于基因治疗避免了细胞移植时繁琐的手术操作,或许在未来基因治疗会有更好的发展前景。
  展望
  现今,越来越多的研究者支持成人心脏存在再生这一观点,并将更多的精力投入到促进心脏再生的研究中。目前以胚胎干细胞和可诱导的多能干细胞为代表的细胞植入治疗已进入临床实验阶段,但关于如何激活心脏内源性的再生能力方面的研究却很少,事实上关于心脏再生的分子调控机制和基因治疗仍有很多未知需要我们去解答。因此,心脏再生领域仍面临许多挑战,但我们相信,随着基础研究的不断深入,心脏再生在临床实践中的应用将会被持续推进。
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