Sian E Harding:国立心肺研究院(NHL)、Imperial大学临床药理学教授,往届国际心脏研究学会(ISHR)欧洲分会主席,AHA/ESC/ISHR理事,研究领域:心力衰竭的心肌细胞功能;调节心肌细胞功能的基因治疗;源自胚胎干细胞的心肌细胞特征及其在心脏修复、组织工程和药物转运中的作用。
《国际循环》:您特别选择了植入LVAD的患者,为什么您对这一人群特别感兴趣?是因为这些患者治疗起来很棘手或治疗手段很有限?还是有其他原因?
<International Circulation>: Why did you have a particular interest in patients with LVADs? Is it because they have limited options?
Harding教授:当然,植入LVAD患者的治疗手段还很有限。因为可以多次取样以便做对照,我们已经在Imperial大学Harefield医院开展了植入LVAD患者的研究。当植入LVAD时,自然会取走一块心肌组织,我们就是从这块组织开始进而分化出心肌细胞。开展SERCA的试验也部分与此有关,因为除了患者得到恢复以外,心肌细胞肌浆网的钙离子转运功能也恢复了。此外,在植入LVAD后也可以取样,例如在患者移植干细胞时,我们显然可以得到心脏各个部位的样本。一项Harefield的队列研究显示患者恢复良好,可以取出LVAD,因此在取出LVAD的同时可以得到小块的心肌样本。这样就可以对植入LVAD前后的情况进行比较。我认为这非常重要,这也是很多试验实际上所欠缺的。如果在试验中观察到益处,那么获得益处的原因又是什么呢?通过比较我们有可能发现细胞是否真的移植成功了,也会知道益处是来自细胞本身的生长还是来自旁分泌作用。
Prof.Harding:They certainly have limited options. At Harefield Hospital in Imperial College we have studied these patients for some time because of the possibility of paired tissue samples. As you implant the LVAD you naturally take a piece of the myocardium and we have been making myocytes from those. Part of the reason the SERCA trial went ahead was because of the evidence from those myocytes that there was restoration of the SR calcium function that went along with recovery. We have also had samples from the LVAD patients when, for example, when they went for transplant and we obtained the entire heart. Also, there was a cohort in Harefield that showed good recovery and the pump was able to be explanted and small samples were obtained at that time and we were able to do a comparison before and after. This is extremely important because evidence that is lacking from many studies is that if you see a benefit what the reason for such a benefit is. So, we have a potential for understanding if we have put cells in, whether it is the cells themselves that have grown or if it is some pericrine idea.