Investigation of the Structural Quality of Bone and Cartilage Repair Following Cell Therapy

使用人体自身的细胞，也就是众所周知的“细胞疗法”，是修复磨损或受损身体部位的一种有吸引力的方法。多年来，我们的中心一直通过使用软骨细胞帮助修复受损软骨区域来帮助膝关节软骨损伤的患者。一些对人类的小型研究表明，干细胞也可以用于修复软骨，也可以帮助修复潜在的骨骼。这两种细胞类型结合在一起可能会有更好的帮助。为了找出答案，慈善机构英国关节炎研究中心正在资助我们的中心进行一项临床试验，比较软骨细胞和干细胞以及这两种细胞类型。这项试验形成了一个独特的机会，不仅可以找出哪种类型的细胞更好，而且还可以找出细胞如何帮助修复以及哪些患者最适合这种治疗。这项拨款申请要求提供资金，以帮助我们了解这些不同类型的细胞，无论是单独的还是组合的，在关节内的表现如何。我们尤其想知道它们如何以正确的方式产生软骨和骨骼，并具有正确的性能来改善膝关节功能。它还将帮助我们事先找出哪些细胞类型对哪个患者最好，或者可能提前确定哪些患者不适合进行细胞治疗。如果是这样的话，他们就不会把希望寄托在这种治疗上了。我们的临床经验告诉我们，细胞治疗的全部益处大约在细胞植入一年后出现。在这个时间点上，我们计划使用一系列技术来识别和量化产生的不同类型的修复组织。这些技术包括核磁共振成像(MRI)，在膝关节手术中对关节本身进行视觉检查，以及在显微镜下检查修复组织的活检组织。MRI可以显示出有多少新的软骨和骨形成，如果新的组织填满了整个受损区域，软骨的表面有多光滑，它与邻近的正常软骨的附着有多好。使用显微镜和其他专门技术的组织学可以显示存在的实际分子，它们是如何排列的，以及细胞是如何行为的。我们将能够比较软骨细胞和干细胞，看看其中一种类型在形成高质量的软骨和/或骨方面是否比另一种类型更好。为了确定细胞疗法对哪些患者不是一个好的选择，我们将测量我们植入的细胞中数千个基因中的哪些基因被激活。通过比较基因和我们在一年内对患者进行的测量，我们希望找到识别这些患者的基因模式。

Using the body's own cells, known as "cell therapy", is an attractive way to repair worn or damaged body parts. For many years, our Centre has help patients who have knee cartilage damage by using cartilage cells to help repair areas of damaged cartilage. A handful of small studies in humans have shown that stem cells could also be used, not only to help repair cartilage, but also to help repair the underlying bone. The two cells types in combination might help even better. To find out, the charity Arthritis Research UK is funding a clinical trial in our Centre to compare cartilage cells versus stem cells versus the two cell types together. This trial forms a unique opportunity to find out not only which type of cell is better, but also how the cells help repair and which patients are best suited for this treatment. This grant application asks for funding to help us finding out how these different cell types, both alone and in combination, behave inside the joint. We especially like to know how they go on to produce cartilage and bone, arranged in the right way, with the right properties to improve knee function. It will also help us to find out beforehand which cell types are best for which patient, or perhaps identify patients beforehand for whom cell therapy is not a good option. If so, it would save them pinning their hopes on this treatment. Our clinical experience has shown us that the full benefit of cell therapy is seen around one year after cell implantation. At this time point we plan to use a range of techniques to identify and quantify the different types of repair tissue produced. These techniques include Magnetic Resonance Imaging (MRI), visual inspection of the joint itself during knee joint surgery, and examining biopsies of repair tissue down the microscope. MRI can show us how much new cartilage and bone have formed, if the new tissue fills the whole damaged area, how smooth the surface of the cartilage is and how well attached it is to the adjacent normal cartilage. Histology using the microscope and other specialised techniques can show the actual molecules which are present, how they are arranged and how the cells are behaving. We will be able to compare cartilage cells and stem cells and see if one type is better than the other at forming good quality cartilage and/or bone. To identify patients for whom cell therapy is not a good option, we will measure which of the thousands of genes are switched on in the cells that we implant. By comparing between the genes and the measurements we do on the patients at one year, we hope to find gene patterns that identify such patients.