●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》：您在心血管疾病的干细胞治疗领域开展了大量工作。能否谈一下这一领域的最新进展，干细胞治疗有哪些优势和障碍？

    <International Circulation>:You have done a lot of work in the area of stem cell therapy for CVD. Can you discuss the latest progress in this area? What are some of the advantages and obstacles to stem cell therapy for CVD?

    Harding教授：我对干细胞移植替代心肌细胞非常感兴趣。我确信目前正在进行的骨髓干细胞试验将证实在某些我本人尚未研究的方面具有益处。我们一直在关注来源于人胚胎干细胞的心肌细胞。尽管美国FDA已经批准Geron公司开展一项相关试验，但是这一技术投入应用还有很多障碍，这是毫无疑问的。诱导性多能干细胞（iPS）很吸引人，因为患者应用时可能不会出现免疫排斥反应，但是我们很想知道是如何做到这一点的。

    目前我们正在研究植入左室辅助装置（LVAD）的患者，LVAD为我们提供了获得细胞的可能，但需要一个相对较长、稳定的时期使细胞成为iPS，随后分化为心肌细胞，然后再应用于LVAD治疗期间，此时患者在LVAD的保护下某种程度上可预防心律失常的增加。我们目前计划在英国开展一项试验，在植入LVAD的情况下进行肌浆网钙-ATP酶（SERCA）基因治疗。

    这种治疗理念就是保持LVAD患者情况稳定，同时有可能在植入LVAD之前和之后获取样本，以使我们真正了解能否获益，且益处是否与植入的细胞有关，还是整体所起作用。目前最吸引人的可能是，很早开展的研究显示可能从心脏成纤维细胞直接分化为心肌细胞，无需经过干预未分化细胞的阶段。Subrastata等发现使成纤维细胞分化为心肌细胞需要三个因素，如果事先考虑到这些因素，我们可能只需将那些因素导入疤痕组织并回收一些心肌细胞。当然，这是将来要做的事情。
 

    Prof.Harding: I am very interested in the possibility of replacing cardiac myocyte. I am pretty sure that the bone marrow trials being conducted at the moment， while being beneficial in some respects， are not doing that. Therefore， I have been looking at the human embryonic stem cell derived myocyte and I think that it is pretty clear that there are very severe barriers to using those; although there is going to be a brain trial from Geron that is FDA regulated.
 

    The induced pluripotent cells have been very interesting for the possibility of immune matching to the patient but I am wondering about the logistics of this. What we are considering is using patients who are being supported on left ventricular assist devices， which gives you the possibility of obtaining cells but having a relatively long and stable interval where it might be possible to make them into iPS， differentiate them into cardiac myocyte， and then reapply them in the context of the LVAD where the patient is protected somewhat from any problems of arrhythmia that might arise. We are doing this particular paradigm with the LVAD for a gene therapy trial on SERCA that we are planning in the UK. The idea is that the LVAD patients will be stable and there is the possibility of obtaining samples from them before and after so you can start to understand if you do get a benefit whether it was due to those cells and whether or not they were integrating and so on.

    The most interesting thing at the moment is probably the very early work coming out showing that it may be possible to go from a fibroblast to a myocyte without the intervening undifferentiated cell stage. I believe it is ???? who has shown that there are three factors what will produce a myocyte from a fibroblast. If you think ahead a little bit from that， there is the possibility of simply introducing those factors into the scar and reclaiming some cardiac myocytes from those， but that is well into the future.