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

细胞治疗后骨和软骨修复结构质量的研究

• 批准号: MR/L010453/1
• 负责人: James Richardson
• 金额: $ 77.8万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL010453%2F1
• 关键词: Investigation; Structural; Quality; Bone; Cartilage

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.

利用人体自身的细胞，被称为“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，我们的中心利用软骨细胞修复受损的软骨区域，帮助患有膝关节软骨损伤的患者。对人类进行的一些小型研究表明，干细胞不仅可以用于帮助修复软骨，还可以用于帮助修复底层骨骼。这两种细胞的结合可能会有更好的帮助。为了找到答案，英国关节炎研究慈善机构资助了我们中心的一项临床试验，比较软骨细胞和干细胞以及两种细胞类型。这项试验提供了一个独特的机会，不仅可以发现哪种类型的细胞更好，还可以发现细胞如何帮助修复，以及哪些患者最适合这种治疗。这项拨款申请要求资助，以帮助我们发现这些不同类型的细胞，无论是单独的还是组合的，如何在关节内表现。我们特别想知道它们是如何产生软骨和骨骼的，以正确的方式排列，具有正确的性能来改善膝盖的功能。它还将帮助我们提前发现哪种细胞类型最适合哪种患者，或者可能提前确定哪些患者不适合细胞疗法。如果是这样，他们就不用把希望寄托在这种治疗上了。我们的临床经验告诉我们，细胞疗法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不同类型的修复组织。这些技术包括磁共振成像（MRI），在膝关节手术中对关节本身的目视检查，以及在显微镜下对修复组织的检查活检。核磁共振成像可以告诉我们有多少新的软骨和骨头形成了，如果新的组织填充了整个受损区域，软骨表面有多光滑，以及它与相邻正常软骨的附着程度如何。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，看看一种细胞是否比另一种细胞更能形成高质量的软骨和/或骨骼。为了确定细胞疗法不适用于哪些患者，我们将测量植入细胞的数千个基因中有哪些被激活。通过比较这些基因和我们一年对病人所做的测量，我们希望找到识别这些病人的基因模式。

项目成果

Development of a Tool to Predict Outcome of Autologous Chondrocyte Implantation.

• DOI: 10.1177/1947603516650002
• 发表时间: 2017-04
• 期刊: Cartilage
• 影响因子: 2.8
• 作者: Dugard MN;Kuiper JH;Parker J;Roberts S;Robinson E;Harrison P;Richardson JB
• 通讯作者: Richardson JB

Aarhus Regenerative Orthopaedics Symposium (AROS).

• DOI: 10.1080/17453674.2017.1297918
• 发表时间: 2016-12
• 期刊: Acta orthopaedica
• 影响因子: 3.7
• 作者: Foldager CB;Bendtsen M;Berg LC;Brinchmann JE;Brittberg M;Bunger C;Canseco J;Chen L;Christensen BB;Colombier P;Deleuran BW;Edwards J;Elmengaard B;Farr J;Gatenholm B;Gomoll AH;Hui JH;Jakobsen RB;Joergensen NL;Kassem M;Koch T;Kold S;Krogsgaard MR;Lauridsen H;Le D;Le Visage C;Lind M;Nygaard JV;Olesen ML;Pedersen M;Rathcke M;Richardson JB;Roberts S;Rölfing JH;Sakai D;Toh WS;Urban J;Spector M
• 通讯作者: Spector M

Osteochondral Lesions of the Ankle Treated with Bone Marrow Concentrate with Hyaluronan and Fibrin: A Single-Centre Study.

用透明质酸和纤维蛋白治疗的脚踝的骨软骨病变：一项单中心研究。

• DOI: 10.3390/cells11040629
• 发表时间: 2022-02-11
• 期刊: Cells
• 影响因子: 6
• 作者: Abas S;Kuiper JH;Roberts S;McCarthy H;Williams M;Bing A;Tins B;Makwana N
• 通讯作者: Makwana N

Perlecan in the Natural and Cell Therapy Repair of Human Adult Articular Cartilage: Can Modifications in This Proteoglycan Be a Novel Therapeutic Approach?

• DOI: 10.3390/biom11010092
• 发表时间: 2021-01-13
• 期刊: Biomolecules
• 影响因子: 5.5
• 作者: Garcia J;McCarthy HS;Kuiper JH;Melrose J;Roberts S
• 通讯作者: Roberts S

Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat.

• DOI: 10.1155/2016/6969726
• 发表时间: 2016
• 期刊: Stem cells international
• 影响因子: 4.3
• 作者: Garcia J;Mennan C;McCarthy HS;Roberts S;Richardson JB;Wright KT
• 通讯作者: Wright KT