Overcoming immunological barriers to regenerative medicine

再生医学领域的目标是替换受损或患病的组织，从而找到治疗目前无法治愈的疾病的方法。目前，似乎有两种不同的方法是可行的：一种是刺激人体自身细胞修复组织，另一种是将新细胞移植到体内。在细胞移植的情况下，一个人可以将细胞从一个人移植到另一个人(同种异体细胞)，就像献血中常见的那样。或者，可以分离患者自己的一小部分皮肤或血细胞，并在实验室将它们转化为称为多能干细胞的细胞，然后这些细胞可以在体内形成任何组织，这样患者就可以用自己的细胞进行治疗。无论采取哪种策略，都必须克服人体的天然免疫防御，才能使治疗取得成功。在异基因细胞的情况下，人体识别出这些细胞是外来的，并将它们杀死--这在献血中不是问题的原因是，人口中有如此多的献血者，可以找到适合不同人的配型。即使潜在的治疗涉及患者自己的细胞，免疫系统也会因组织损伤而被激发，导致炎症，身体的免疫细胞对危险信号做出反应，吞噬移植的细胞。我们召集了一个来自不同背景的研究团队合作，以找到控制免疫系统的新方法，使再生医学治疗更有效。我们的团队包括在器官移植领域拥有多年经验的研究人员，他们正在开发减少免疫抑制药物需求的方法，还有一些研究人员已经在进行细胞移植的临床试验，以治愈某些形式的失明和肝功能衰竭。我们也有比较细胞移植或内源性修复是治疗心力衰竭更好方法的专家，还有免疫学、多能干细胞和成人组织细胞的专家。我们已经着手回答在再生医学中至关重要的三个问题。我们希望确定移植细胞分泌的与免疫系统通信的蛋白质，并发现不同类型的细胞是否会产生不同的信号。可能是肝细胞对眼睛细胞产生了不同的信号，或者如果肝细胞来自成人而不是多能干细胞，就会产生不同的信号。这些信息将帮助我们决定来自一种来源的细胞是否比来自另一种来源的细胞更适合移植，并将为我们提供关于保护细胞免受免疫攻击的最佳方法的线索。下一个问题是，我们认定的可能导致移植失败的信号是否可以被阻断，例如，通过在细胞上覆盖一种蛋白质来保护它们免受攻击，或者通过将由多能干细胞产生的免疫细胞移植回来。最后一个问题是，炎症如何促进内源性修复并影响移植细胞的命运。我们将识别不同类型的炎症细胞，然后检查破坏每种细胞类型是改善还是恶化组织修复。我们的研究最终将导致改进失明、心力衰竭、肝功能衰竭和炎症性肠病的治疗。我们的发现将与其他研究人员分享，这样他们就可以将我们的观察、实验技能和工具应用于其他重要的疾病。我们认为，具有非常不同观点的研究人员之间的合作提供了利用人体免疫系统使治疗更有效的最佳机会。

The goal of the field of regenerative medicine is to replace damaged or diseased tissue and thereby find cures for diseases that are currently untreatable. At present two different approaches appear feasible: one is to stimulate the body's own cells to repair the tissue and the other is to transplant new cells into the body. In the case of cell transplantation one could transplant cells from one individual to another (allogeneic cells), as happens routinely in blood donation. Alternatively, one could isolate a small number of a patient's own skin or blood cells and convert them in the lab into cells called pluripotent stem cells that can then form any tissue in the body, so that patients can be treated with their own cells. No matter which strategy is taken, it is essential to overcome the body's natural immune defences in order for the treatment to succeed. In the case of allogeneic cells, the body recognises that the cells as foreign and kills them - the reason why this is not a problem in blood donation is that there are so many donors in the population that good matches for different individuals can be found. Even when the potential treatment involves the patient's own cells, the immune system can be provoked in response to tissue damage, resulting in inflammation whereby immune cells of the body respond to danger signals and engulf the transplanted cells.We have assembled a team of researchers from different backgrounds to collaborate in order to find new ways to control the immune system to make regenerative medicine treatments more effective. Our team includes researchers with many years' experience in organ transplantation, who are developing ways of reducing the need for immunosuppressive drugs, and researchers who are already carrying out clinical trials of cell transplantation to cure certain forms of blindness and liver failure. We also have experts who are comparing whether cell transplantation or endogenous repair are better approaches for treating heart failure, experts in immunology, pluripotent stem cells and cells from adult tissues. We have set out to answer three questions that are of central importance in regenerative medicine. We want to identify the proteins that transplanted cells secrete to communicate with the immune system and discover whether different cell types produce different signals. It might be that liver cells produce different signals to eye cells, or that liver cells produce different signals if they have come from an adult rather than a pluripotent stem cell. This information will help us decide whether cells from one source might be better for transplantation than those from another source, and will also give us clues about the best ways to protect the cells from immune attack. The next question is whether the signals we identify as potentially contributing to transplant failure can be blocked, for example by coating cells with a protein that protects them from attack or by transplanting back immune cells generated from pluripotent stem cells. The final question is how inflammation contributes to endogenous repair and influences the fate of transplanted cells. We will identify different types of inflammatory cell and then examine whether destroying each cell type improves or worsens tissue repair.Our research will lead eventually to improved treatments for blindness, heart failure, liver failure and inflammatory bowel disease. Our discoveries will be shared with other researchers, so that they can apply our observations, experimental skills and tools to other important diseases. We believe that collaborations amongst researchers with very different perspectives offer the best opportunity to harness the body's immune system to make treatments more effective.