<International Circulation>: Critical limb ischemia (CLI) is a common and devastating manifestation of peripheral arterial disease and in the past there have been difficulties encountered in its prevention and treatment. There has been a lot of emphasis and expectations put on future therapies. What is there to look forward to?
   《国际循环》：重症肢体缺血是一种常见的致残性外周动脉疾病，当前在预防和治疗方面都存在很多困难。我们寄希望于未来新的治疗手段出现，您认为将来的发展方向会是怎样？
    Prof. Emmerich: When there is no possibility of revascularization， which is the standard of care for CLI， there is no medication which is useful in this situation. There have been big developments in terms of an approach to try to stimulate angiogenesis and this approach is of two kinds. The first one is to try to stimulate angiogenesis by gene therapy and the second one is to stimulate angiogenesis or vasculogenesis by cell therapy. In the first case there are several trials that were conducted without control groups， which used different gene approaches but mainly using Vascular Endothelial
    Growth Factor (VEGF) or FGF-1 to try to stimulate angiogenesis. All of these trials have included more than 500 patients and demonstrated that: it is a safe procedure; that it seems to generate new vascularization; and decrease pain and increase healing. There are only two small randomized trials. One of them was negative but there were more responders in the group receiving gene therapy. The second trial， called the Talisman Study， demonstrated an improvement in the gene therapy group with a 50% decrease in the rate of major amputation. This result needs to be confirmed by another ongoing trial， called the TAMARIS trial whose results will be available soon. If there is an improvement seen using gene therapy in this trial， in this case FGF-1， it will be a very important step forward. It is an easy procedure to perform. It requires only a few intramuscular injections every two weeks and would be an excellent improvement in the management of CLI. The second approach is cell therapy which was initiated eight years ago by Tateishi-Yuyama et al. It was demonstrated that IM injection of bone marrow mononuclear cells is able to stimulate angiogenesis. This approach was also performed in many uncontrolled trials that include more than 750 patients were treated in these trials. It was also demonstrated to be safe and that you can generate new vascularization. There are only a few randomized trials， which we cannot take into consideration， to really indicate that cell therapy is better than usual care. By the way， there are several (six or seven) randomized trials underway with the goal of trying to demonstrate that cell therapy is more efficient than usual care in CLI. So if this approach is also positive， it will be very important to the field of CLI.
    Emmerich教授：当不能开展血管成形术时，重症肢体缺血的治疗标准，在没有可用的药物这种情况下，未来将会有很大的发明：通过刺激血管再生的方式，方式有两种：第一个是通过基因治疗试图刺激血管再生，第二个是通过细胞治疗使血管再生成或血管再通，在第1种情形中，我们已经做了一些没有对照的相关试验，它通过基因的路径，但是主要靠血管内皮增长因子或FGF-1去刺激血管再生，所有的这些实验包含了超过500个病人并且证明了：这是一个安全的过程，它看上去在生成新的血管，并且减少了痛苦增加了治愈，现在有两个小型的随机试验，他们中的一个是否定的，尽管接受基因治疗的队伍中有很多反应。第二项试验，被称为Talisman研究，证明了一项进步，在基因治疗组中，大的切断阻滞大约有50%的下降。这个研究结果需要另一个正在进行的试验来证明。这个被称为TAMARIS的试验结果将变得有用。在这个试验中如果使用基因疗法看上去有进步，那么在这个条件下的血管内皮增长因子1，将会变成前进的重要步骤。这同时有一个简单的过程需要执行，需要每两周少量肌肉注射，在处理重症肢体缺血中将会变成出色的改进。第二种方法是细胞治疗开始于八年前的Tateishi-Yuyama等.他被证明骨髓的单核细胞的肌内注射可以能够刺激血管再生，这个方法同时也被许多的非控制实验所进行，包括超过750病人在这些实验中被治疗。试验同时被证明是安全的和可以产生新的新生血管。这仅仅是一些我们所不能够考虑的随机试验，事实上表明细胞治疗比常规治疗更好，顺便说一下，这儿有一些（6或7）随即试验正在进行中，目的是试图证明细胞治疗在 CLI中比常规治疗更有效，因此如果这个路径是积极的，那么将对CLI的领域是十分重要的。