Stuart Forbes教授
爱丁堡大学移植和炎症研究所
Hepatology Digest: The use of stem cells has been seen as a potential alternative for liver transplantation. What have been the latest developments in bridging laboratory experimentation to practical clinical settings?
《国际肝病》：干细胞目前已经被视为肝移植潜在的替代选择。您认为近期在从实验室研究到临床实践的转化方面有哪些最新的进展？
Prof. Forbes:Based on our findings we have been trying to take the next step in trying to use these cells in humans based on the findings from rodent and in vitro models. The work done in animal models have shown that bone marrow derived stem cells can be used to promote liver regeneration and reduce liver fibrosis. This is encouraging since it could mean that autologous bone marrow therapy is an avenue which can be applied to humans without too many practical or regulatory barriers. Indeed， there are a number of small non randomized studies published on bone marrow therapy to promote liver regeneration from a number of groups around the world. From our group we are about to commence a randomized study on hematopoietic stem cell therapy for liver cirrhosis in conjunction with Dr Phil Newsome of the University of Birmingham called the REALISTIC Study. This is a study comparing no therapy against G-CSF (Granulocyte colony stimulating factor) and G-CSF plus hematopoietic stem cells. Hopefully after this study we will have a clearer understanding if there is a true clinical benefit from this therapy.
Forbes教授：我们在前期干细胞研究成果的基础上，目前正致力于将哺乳动物和体外模型的发现应用到人体。动物试验显示，骨髓来源的干细胞可促进肝再生和减少肝纤维化。这就意味着自体骨髓治疗是一条可行的途径，可用于人体，而且没有太多实用性和调节方面的问题，令人振奋。事实上，全世界已有多个小组发表了一些小型非随机研究，结果显示骨髓治疗可用于促进肝脏再生。我们小组与伯明翰大学的Phil Newsome博士合作，正在着手开始一项采用造血多能干细胞治疗肝硬化的随机研究，名为REALISTIC 研究，对比无针对G-CSF（粒细胞集落刺激因子）的治疗方案与G-CSF联合造血干细胞治疗的疗效。希望这项研究完成后我们可以对干细胞治疗的临床益处有一个更为清晰的认识。
Hepatology Digest: There are certainly various types of stem cells we can use and is there a particular preference you have and why?
《国际肝病》：目前有很多类型的干细胞可用，您有没有倾向于哪一种干细胞，为什么？
Prof. Forbes；The use of stem cells is still quite a controversial area. Some groups are using mesenchymal stem cells to promote liver regeneration and reduce liver fibrosis. However， we have found that they can form into scar forming cells in the liver and so we have been a little cautious in this direction. On the other side it may be that mesenchymal cells are anti fibrotic and anti inflammatory in the liver. Again we need to translate the findings from animal models into clinical studies. From ourselves we have found that stem cells of the hematopoietic lineage including cells from the monocyte macrophage lineage have been important in controlling liver regeneration and liver fibrosis in a pro and anti fibrotic way. The key is to understand which situations will cause the monocyte macrophages to act in an anti fibrotic pro regenerative sense.
Forbes教授：干细胞治疗仍是一个极具争议的领域。一些小组采用间充质干细胞促进肝脏再生和减少肝纤维化，但是我们发现这类干细胞在肝内可以分化成成纤维细胞，因此我们有些顾虑。而也有研究提示这类干细胞可能在肝脏发挥抗纤维化和抗炎作用。这些来自动物模型的发现还需要转化到临床。我们自己的研究发现造血干细胞，包括单核巨噬系来源的细胞，在促进肝脏再生和抗纤维化方面很重要，但关键要了解何种情况可以刺激单核巨噬细胞发挥抗纤维化促再生作用。
Hepatology Digest: It has been reported that monocytes and macrophages might have both benefits and problems as candidates for stem cell therapy. How would you tackle these points when you use them in humans?
《国际肝病》：已有报道单核巨噬细胞作为干细胞治疗的候选细胞，利弊各半。若您将这类细胞用于人体，将如何权衡利弊？
Prof. Forbes: We must be very cautious in this respect; clearly when translating work done in animal models into humans a step wise approach must always be followed. This perhaps can be done by first using the cells in phase 1 pilot studies where we study the patients very closely to see if there are any safety concerns. Should there be no major problems and results prove encouraging then this will give us an incentive to enroll more patients for larger more advanced randomized controlled studies where we can look more definitively for an answer.
Forbes教授：这方面显然要非常慎重，通常将动物试验的成果转化到人体时必须遵循下述比较明智的步骤。首先进行1期试验，密切观察安全性。若没有大的安全问题，且结果确实令人振奋，则招募更多病人扩大规模进入随机对照研究，以进一步明确治疗的安全性问题。
Hepatology Digest: Amniotic fluid is said to contain a wide variety of useful cells. Could you comment about obtaining cells in this manner?
《国际肝病》：羊水里含有多种有价值的干细胞，能否请您就这种获取干细胞的方式做一评论？
Prof. Forbes: Many cell types now are seen as a worthwhile and potent source of stem cells for organ regeneration. This has been shown particularly by the work of Professor Shinya Yamanaka who has shown that somatic cells can be turned into embryonic stem like cells the so called iPS (Induced pluripotent stem) cells from these all starting cell types may have potential to be clonogenic in that they can produce large numbers of cells and then into many different tissue types. The key to all these starting cell types is whether they provide cells which can differentiate in a reliable manner coupled with being growth controlled so that they do not result in any detrimental effects when they are injected into patients.
Forbes教授：多种类型的干细胞都可作为干细胞有价值的强大来源用于治疗肝再生。特别是日本的Shinya Yamanaka教授，他的研究显示，体细胞可被诱导成胚胎干细胞样的细胞，即所谓iPS（诱导的多能干细胞），这些起始的iPS细胞有集落形成潜能，可产生大量细胞，分化为不同的组织类型。这类细胞的重要性在于其分化和生长模式可以控制，注射入体内后不会产生有害效应。
