International Circulation: Thank you Dr. Willerson and Dr. JunBo Ge for joining us today at ACC. The first question Dr Willerson， you have done a lot of work in stem cells and vulnerable plaque etc， can you give as a little introduction perhaps to some of the information you might be presenting today and some of your most recent work in this area?
《国际循环》：非常感谢James T. Willerson教授和葛均波教授参加此次ACC大会。我想问Willerson教授，您在干细胞和易损伤斑块领域做了很多研究，是否简要介绍一下在今天大会中将要演讲的题目以及您近期在此领域的研究成果？

Prof. Willerson: Well I will be talking about stem cells and their ability to help repair injured human hearts. I am going to point out that a variety of different human adult stem cells are capable of contributing to repair in patients with chronic coronary heart disease and heart failure， and that includes the bone marrow-derived mononuclear cells; the CD34 + cells; the mesenchymal and pro-mesenchymal cells. All are capable of improving blood flow to the human heart and when they are functionally viable， that is when they can form colonies in culture， they also improve the function of the heart. One of the things we found recently is that older human cells taken from the bone marrow in patients with heart failure sometimes are sick themselves， the stem cells are sick. They don’t form colonies in culture and when they are injected into the human heart， they don’t work very well， but when they are capable of renewing themselves and they are put into the human heart， they improve blood flow and they improve function.
Willerson教授：好的，我的演讲主要涉及干细胞及其参与人类心肌损伤修复的功能。我认为有很多种类不同的人成人干细胞可以参与慢性冠心患者和心衰患者的心肌损伤修复，这其中包括骨髓来源单核细胞、CD34+细胞、间充质细胞和前间充质细胞。所有细胞均可以提升心肌血流灌注，当其均有功能活性时，即可在培养过程中形成菌落时，也可改善心脏功能。我们近期发现的一个现象，心衰患者骨髓中提取的衰老人类细胞也是病态的，也就是说干细胞也是病态的。这些细胞在培养时不能形成菌落，将其注射进人类心脏时效果也不好，但当其可自我更新时注入心脏，却可以改善血流和心脏功能。

Prof. JunBo Ge: Dr Willerson， I have been in charge of the stem cell centre in Fudan University in Shanghai， and our group also has done some research on stem cells. The key issue is， I think at this moment， we try to culture or we try to develop myocyte or myocyte-like cells and we transplant this kind of cell in the heart but it seems these cells do not work very well， but one might believe it is just like a kid. If he is born in China and when newborn put in America， in this environment he can speak perfect English but if we put an adult in America he has to learn how to pronounce. I think， for the peripheral vessels， repair may be no problem， but for the myocardium this has trouble because the myocardium has its own potential for conduction and contraction. Do you believe so?
葛均波教授：Willerson教授，我负责上海复旦大学干细胞研究中心，我们的研究组也做了些有关干细胞的研究。目前的关键问题是，我们试图去培养发育心肌细胞或心肌细胞样细胞，然后我们将此类细胞移植入心脏，但这些细胞似乎并不能起到作用，但大家还是要把它看作一个孩子，如果他生在中国但从小在美国长大他能说流利的英语，但如果把他成年后在放到美国，他也只能从发音开始学。我认为对外周血管而言，修复不成问题，但对心肌有很大问题，因为心肌有潜在的传导和收缩功能。您怎么认为？

Prof. Willerson:The adult human stem cells promote perfusion increases primarily. The CD34+ cells and mesenchymal cells contribute to perfusion. We’ve shown that the CD34+ cells can fuse to injured murine cells in an experimental infarct model and one uses SCID mice that can’t reject the cells. When they fuse， they can reversibly injure cells， it turns on the cell cycle and a new cell is born from that fusion phenomenon. So the CD34+ cells can participate in myogenesis through the fusion phenomenon. It occurs at a low level though and one’s either going to have to promote that at a higher level， the receptors for the fusion， for a alpha-4 beta-1 VCAM receptor. One is either going to have to promote the fusion at a higher level by over-expressing these receptors or identify or create cells that will become myocytes. I’m very excited about the engineering of cells， fibroblasts. We have been working on this， Dr Robert Schwartz at our institution working with Dr Edward Yeh and myself， and we are taking human skin fibroblasts and over-expressing the cardiac genes involved in the development of myocytes. And we have done that now and the fibroblasts now express the cardiac genes involved in the development of myocytes. We are just beginning to study those cells in the SCID  mouse model in an experimently created infarct and I think that’s going to allow a generation of myocytes at a higher level. Adult cells already promote perfusion at a lower level， some of them promote myogenesis， but I think combinations of these kinds of cells will probably be very effective. Then we need know a lot about the embryonic cells and be able to select out the cell root which promotes myogenesis. That may be more difficult than it would seem…..
Willerson教授：成人干细胞主要提高血流灌注。CD34+细胞和间充质细胞也有利于灌注。我们已经发现CD34+细胞在体外心梗模型中可以融入受损伤的小鼠细胞，且有人应用SCID小鼠也不能排斥细胞。当他们融合时，可逆转损伤细胞，开启细胞周期，并使一个新的细胞从融合现象中产生。所以CD34+细胞可通过融合现象参与心肌细胞生成。但其发生水平仍较低，要么需要促其发展，将发生水平提高。对融合受体，如α4β1VCAM受体，要么通过过度表达这些受体或识别或创造可分化为心肌细胞的细胞来促进融合。我对成纤维细胞非常看好——我把它看作细胞工程师。我们研究所的Robert Schwartz和Edward Yeh教授还有我目前正在进行这方面研究，我们取人皮肤成纤维细胞并将参与心肌细胞形成的心脏基因过度表达。我们目前已经将该步骤完成，成纤维细胞现在已经表达了参与心肌细胞形成的心脏基因。我们也开始研究这些细胞在SCID小鼠模型中构建的实验诱导梗死中的作用，我想会出现较多心肌细胞生成。成人细胞可低水平促进灌注，有些可以促进心肌细胞生成，但我认为将这些细胞结合起来可能更为有效。介时，我们可能需要更多地了解胚胎细胞并选择出促进心肌细胞生成的根源细胞。当然，这远比想象的难很多……

Prof. JunBo Ge: I do believe we need a multi-potent cell， a stem cell in this environment either to develop to a myocyte or to some vessels. We don’t need a mature cell in the culture like a myocardial cell to inject to the cell because it will not follow the steps maybe.
葛均波教授：我相信我们需要多能细胞，也即在此环境下衍变成心肌细胞或血管。我们不需要培养中的成熟细胞，如心肌细胞，将其注入后可能并不会按照我们预想的进行细胞分化。

Prof. Willerson:: Originally， the belief was that one would have to have embryonic cells， but the surprise has been， and this is from our work and Zeiher’s work in Germany， that the adult cells can do quite a bit and they clearly improve blood flow when they are functionally normal……
Willerson教授：一开始的观点认为必须要有胚胎细胞，但是令人惊喜的事情出现了，这也是我们和德国Zeiher教授发现的，也就是成人细胞也可加以利用并且当其功能正常时也可促进血流……

Prof. JunBo Ge: I mean the myocyte should develop in this environment not in culture， not a mature cell to transfer to myocardium. I think we need a cell which can develop in this environment which will work better.
葛均波教授：我的意思是心肌细胞应该在这样的环境下生长而非在培养环境下，不将成熟细胞转移至心肌。我认为我们需要可在这样环境下生长的细胞。

Prof. Willerson: We’ll see. It may not. Engineered cells we are very optim