Timothy D. Henry教授  美国Abbott西北医院

　　<International Circulation>: Let’s start with cell therapy. Could you please talk about some of the most current clinical applications?

　　《国际循环》:我们从细胞疗法方面开始采访。您能谈一谈目前细胞疗法的最新临床应用情况吗？

　　Prof. Henry: I think CV therapy currently is at a key moment in history. It’s a therapy whose potential we have all been excited about for a variety of CV conditions. Acute MI， congestive HF， refractory ischemia， and peripheral arterial disease for both critical ischemia and claudication. All of these trials in these areas have completed Phase I and II smoothly. In general， they have been certainly positive. In each of these areas， we have progressed to the point where we have adequately powered， large， mutli-center Phase II trials. It is a very important time in cell therapy. Another important issue with cell therapy is that the majority of the research has been done as with bone marrow mononuclear cells. I could call these the first generation. We know that the principal problem with BMM cells is that， as we get older， the number of stem cells and the potency of our stem cells decline. We have a number of trials over that last few years that have demonstrated that. Most noticeably， the FOCUS on HF trials， which was published in JAMA in November. This trials demonstrated that bone marrow in ischemic HF had an improvement in EF. The primary endpoints， which were volumes and MVO2 where negative， but the EF was better. More importantly， if you look inside the numbers， you will find that the older people had less response or no response， where as younger people had a response. Likewise， if you had good cells-if they were CD34 positive or CD133 positive-correlated with improvement in EF.  This is a glimpse that the type of cell matters. One of the key things going forward is to improve on bone marrow cells.

　　Henry教授: 我认为目前心血管治疗正处于关键时期，该疗法极具潜力，对于将其应用于各种心血管疾病，如急性心肌梗死、充血性心力衰竭、难治性缺血性疾病及外周动脉疾病（重症下肢缺血和跛行）的治疗，我们非常激动。目前，该领域研究均处于较稳定的临床I、II期，大致呈出阳性结果。我们也希望这些试验都能进展到实力充足、规模庞大且多中心的临床II期，对细胞疗法非常重要。另一个严重问题是，目前大多数研究采用骨髓单核细胞（BMMs），我将其称为第1代移植细胞。这种细胞随年龄增长，干细胞数量及功能逐渐降低。一些持续数年的研究已证实这一点，最显著的是立足于心力衰竭的FOCUS研究，该研究结果于去年11月发表在JAMA杂志。研究显示，缺血性心力衰竭患者应用BMMs输注治疗可明显改善射血分数。虽然FOCUS研究主要终点--左心室收缩末期容积和最大耗氧量并未显著改变，但射血分数却有所好转。最重要的是，如果对研究数据进一步分析，会发现老年人对BMMs输注疗法反应较差或基本无反应，而年轻人却反应明显。同样，如果采用优质的CD34+或CD133+细胞移植治疗，患者射血分数同样可得到改善。以上就是细胞疗法概览，未来的关键仍是如何改善骨髓单核细胞输注疗法。

　　<International Circulation>: One of the key factors is age， why aren’t you just using younger transplants?

　　《国际循环》:其中一个关键因素是年龄，为何您不选用更为年轻的受试者？

　　Prof. Henry: There is a number of strategies. One is to give more cells. There are companies that， instead of giving a million or a hundred million cells， will give a billion. A second strategy， is to give selected cells; by choosing CD34+， CD133+， or ADL-bright cells. They would all be autologus cells， but they would be selected for their stem cell potency. They would be selected to perform a variety of tasks. One would be for endothelial progenitor cells; there would others for mayo-genesis. A third way to do bone marrow is to alter it. There are several trials， such as C-CURE trial， that used bone marrow and enhanced the cell product. A fourth potential is to use allergenic cells from young， healthy donors. That will not work for all types of cells， but for mesenchyma cells， it will. A fifth approach would be to use cardiac-derived cells. There is a lot of interest in this. There are two trials， one is called the CADUCEUS trial published last year and SCIPIO trial， both used cardiac-derived cells. What is happening in the Phase I and II is that there is this new generation of cells that we can enhance the efficacy of. Clearly， we already have outstanding safety. Where are we close to application? In Europe， the BAMI trial is set to start. This is a large， randomized， placebo-controlled trial that will look at bone marrow mononuclear cells for acute MI.  In refractory angina， Baxter is sponsoring the RENEW trial. This again is a large， double-blind， placebo-controlled trial in patients who are not candidates for further revascularization. In HF， there is a series of last Phase II and Phase III trials with a variety of different agents. Likewise， in critical ischemia there is a variety of trials. What are our challenges? The biggest challenge is to coordinate all of the critical trials that are being done. There are a huge number of trials， but the problem too often is that they are too small or not well designed. From an international standpoint， our challenge is to create high-powered studies that can show the true safety and efficacy of these projects.

　　Henry教授：细胞疗法有一系列治疗方案。首先可以输注更多细胞，这不单指输入百万或几亿单位，而是十亿单位细胞。其次，可输入特定细胞，如CD34+、CD133+或ADL-bright 细胞。这些虽然是自体细胞，但却因具有干细胞功能而被挑选进行多种治疗，例如，内皮祖细胞、生肌细胞等。第三，可以进行骨髓移植。有不少试验，如C-CURE，通过骨髓移植提高细胞生成率。第4个方案是移植健康年轻人的异基因细胞，并非所有细胞均可移植，这种治疗只适用于间质细胞。第5个方案是使用心脏祖细胞，这是目前研究热点。已发表的CADUCEUS 试验和SCIPIO试验均利用心肌祖细胞。通过I和II期临床试验证实，新一代细胞可增强疗效。显然，细胞移植的安全性极高，那如何将之应用于临床治疗？在欧洲，BAMI临床试验已启动，这是一项大型、随机、安慰剂对照研究，旨在观察骨髓单核细胞对急性心肌梗死的疗效。此外，Baxter公司赞助的对难治性心绞痛的RENEW研究，同样是大型、双盲、安慰剂对照试验，针对无需接受进一步血运重建的患者。心力衰竭方面也已开展针对不同治疗药物的II期和III期临床试验。同样，关于恶性心肌缺血研究也很多。当前最主要问题是，所有关键试验还在进行中。尽管有大量试验，但大多存在规模小和方案设计不完善的缺点。从全球角度看，我们的挑战是开展高效研究以体现上述治疗方案的真实安全性和有效性。