Pathfinder: How do cartilage injuries heal naturally? An experimental study in humans

探路者：软骨损伤如何自然愈合？

• 批准号: MR/N02706X/1
• 负责人: Jan Herman Kuiper
• 金额: $ 62.28万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN02706X%2F1
• 关键词: Pathfinder; How; do; cartilage; injuries

Osteoarthritis is a very common disease of the joints, for which in the United Kingdom alone almost 9 million people have sought treatment. Osteoarthritis causes severe pain, stiffness and makes the patient less able to go about their daily physical activities. Osteoarthritis is a disease of the joint and affects the cartilage inside the joint and the bone at the joint. Many factors are known to increase the risk of getting osteoarthritis, or the rate at which it gets worse. Very important among these factors is an injury or a defect of the cartilage. More than 250 years ago, a famous surgeon presented a paper at the Royal Society of London explaining that cartilage, once injured, does not heal. Since those days, doctors and scientists have thought that this is indeed the case. Nobody was therefore surprised that having a cartilage injury or defect is so dangerous when it comes to osteoarthritis. Research from the past 10 years is now throwing doubt on this old certainty. Researchers who took regular scans of volunteers over time noted that sometimes these defects come and then go. Surgeons often see these defects when they reconstruct a ruptured knee ligament, a common sports injury. A Japanese group of surgeons decided to look again after a year to see what had happened to these defects, and noted that about half of them had got better! Cartilage defects in human therefore can heal, but nobody knows how this works. A large number of doctors and surgeons are therefore trying to find out how it works, using animal experiments. But a human is not an animal. Besides the fact that we walk on two instead of four legs, the healing of these defects in humans seems far better than in animals. For many years, our Centre has helped patients who have knee cartilage damage by using the patients' own cartilage cells to help repair areas of damaged cartilage. This form of treatment using the body's own cells is known as "cell therapy". The treatment starts by taking a piece of cartilage about the size of a peanut (10 mm) from the patient's knee. We never treat this defect, but if we look again after a year, this 10 mm defect has always healed, all by itself. This is therefore another example of a naturally healing cartilage defect. Because we create the defect and can then follow how it heals over time, it will form an ideal way to study cartilage healing in humans. Our proposal is therefore to use our cell therapy patients as a human experimental model of natural cartilage healing. We plan to use a wide range of techniques to study, identify and quantify the way in which cartilage heals. These techniques include Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT), visual inspection of the joint itself during knee joint surgery, examining biopsies of repair tissue down the microscope and measuring various kinds of molecules researchers think are important. MRI, PET and CT can show us where the cells that make new cartilage are active, 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. Besides our cell therapy patients, where all defects heal, we will also study a group of ligament reconstruction patients with cartilage defects. Only half of those will heal, so we can compare between the groups and perhaps understand more about what controls natural cartilage healing.

骨关节炎是一种非常常见的关节疾病，仅在英国就有近900万人寻求治疗。骨关节炎会导致严重的疼痛，僵硬，使患者无法进行日常身体活动。骨关节炎是一种关节疾病，影响关节内的软骨和关节处的骨。已知许多因素会增加患骨关节炎的风险，或增加其恶化的速度。这些因素中非常重要的是软骨的损伤或缺陷。250多年前，一位著名的外科医生在伦敦的皇家学会上发表了一篇论文，解释说软骨一旦受伤就不会愈合。从那时起，医生和科学家就认为情况确实如此。因此，没有人感到惊讶，软骨损伤或缺陷是如此危险，当谈到骨关节炎。过去10年的研究现在对这一古老的确定性提出了质疑。研究人员对志愿者进行了定期扫描，发现这些缺陷有时会出现然后消失。外科医生在重建膝关节韧带断裂时经常会看到这些缺陷，这是一种常见的运动损伤。一组日本外科医生决定在一年后再次检查这些缺陷，并注意到其中约有一半已经好转！因此，人类的骨骼缺陷可以治愈，但没有人知道这是如何工作的。因此，大量的医生和外科医生试图通过动物实验来找出它是如何工作的。但人不是动物。除了我们用两条腿而不是四条腿走路之外，人类的这些缺陷的愈合似乎比动物好得多。多年来，我们的中心通过使用患者自身的软骨细胞来帮助修复受损软骨区域，从而帮助膝关节软骨损伤的患者。这种使用人体自身细胞的治疗形式被称为“细胞疗法”。治疗首先从病人的膝盖上取下一块花生大小（10毫米）的软骨。我们从来没有治疗过这个缺陷，但如果我们在一年后再次观察，这个10 mm的缺陷总是会自行愈合。因此，这是自然愈合软骨缺损的另一个例子。因为我们创造了缺陷，然后可以跟踪它如何随着时间的推移而愈合，这将成为研究人类软骨愈合的理想方法。因此，我们的建议是使用我们的细胞治疗患者作为自然软骨愈合的人类实验模型。我们计划使用广泛的技术来研究，识别和量化软骨愈合的方式。这些技术包括磁共振成像（MRI），正电子发射断层扫描（PET），计算机断层扫描（CT），膝关节手术期间关节本身的目视检查，在显微镜下检查修复组织的活检，以及测量研究人员认为重要的各种分子。MRI，PET和CT可以告诉我们制造新软骨的细胞在哪里活跃，形成了多少新软骨和骨骼，如果新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业技术的组织学可以显示存在的实际分子，它们如何排列以及细胞如何行为。除了我们的细胞治疗患者，所有的缺陷愈合，我们还将研究一组韧带重建软骨缺损的患者。只有一半的人会愈合，所以我们可以在各组之间进行比较，也许可以更多地了解是什么控制了自然软骨愈合。

项目成果

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

Autologous chondrocyte implantation in osteochondral defects of the talus: Two to Fourteen Year Follow-up study

自体软骨细胞植入治疗距骨骨软骨缺损：二至十四年的随访研究

• 发表时间: 2022
• 作者: Devany A

Proteomic Analyses of Autologous Chondrocyte Implantation Plasma Highlight Cartilage Acidic Protein 1 as a Candidate for Preclinical Screening.

• DOI: 10.1177/03635465231156616
• 发表时间: 2023-05
• 期刊: The American journal of sports medicine

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

The Effect of Affect: Does a Patient's Outlook Influence Their Recovery?

影响的影响：患者的前景会影响他们的康复吗？

• 发表时间: 2019
• 作者: Hopkins, T