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.

使用人体自己的细胞（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，我们的中心一直在帮助那些通过使用软骨细胞来帮助修复软骨受损区域的患者。在人类中进行的一些小型研究表明，还可以使用干细胞，不仅有助于修复软骨，还可以帮助修复基础骨骼。组合组合的两种细胞类型可能会有所帮助。为了发现，英国慈善关节炎研究正在为我们中心的一项临床试验提供资金，以将软骨细胞与干细胞与两种细胞类型进行比较。该试验构成了一个独特的机会，不仅要找出哪种类型的细胞更好，还可以找到细胞如何帮助修复以及最适合该治疗的患者。该赠款申请要求资金帮助我们找出关节内部的这些不同的细胞类型如何单独和联合使用。我们特别想知道它们如何继续产生软骨和骨骼，并以正确的方式排列，具有正确的特性来提高膝盖功能。它还将帮助我们事先找出哪种细胞类型最适合哪种患者，或者可能事先识别患者的细胞疗法不是一个不错的选择。如果是这样，这将节省他们将希望固定在这种治疗上。我们的临床经验向我们表明，细胞植入后一年大约可以看到细胞疗法的全部益处。此时，我们计划使用一系列技术来识别和量化所产生的不同类型的修复组织。这些技术包括磁共振成像（MRI），膝关节手术期间关节本身的视觉检查以及检查显微镜下的修复组织活检。 MRI可以向我们展示，如果新组织填补了整个损坏的区域，软骨表面的光滑程度以及与邻近的正常软骨的附着程度。使用显微镜和其他专业技术的组织学可以显示存在的实际分子，它们的排列方式以及细胞的行为方式。我们将能够比较软骨细胞和干细胞，并查看一种类型是否比另一种形成优质软骨和/或骨骼更好。为了确定细胞疗法不是一个不错的选择的患者，我们将测量我们植入的细胞中成千上万基因中的哪个基因中的哪个。通过比较我们一年对患者的基因和测量结果，我们希望找到鉴定此类患者的基因模式。

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.

• 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

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

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