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

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。骨关节炎会导致剧烈的疼痛、僵硬，并使患者不能进行日常的身体活动。骨关节炎是一种关节疾病，会影响关节内的软骨和关节处的骨骼。众所周知，许多因素都会增加患骨性关节炎的风险，或者说病情恶化的速度。在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皇家学会发表了一篇论文，解释说软骨一旦受伤就无法愈合。自那时以来，医生和科学家一直认为情况确实如此。因此，当涉及到骨关节炎时，软骨损伤或缺陷是如此危险，没有人感到惊讶。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一段时间的定期扫描，他们注意到，有时这些缺陷来了又走。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，看看这些缺陷发生了什么，并注意到大约一半的缺陷已经好转！因此，人类的软骨缺陷可以愈合，但没有人知道这是如何起作用的。因此，大量的医生和外科医生正试图通过动物实验来找出它是如何工作的。但人类不是动物。除了我们用两条腿而不是四条腿走路这一事实外，人类对这些缺陷的修复似乎比动物要好得多。多年来，我们的中心一直通过使用患者自己的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。这种利用人体自身细胞进行治疗的形式被称为“细胞疗法”。治疗首先从患者的膝盖上取出一块花生大小(10毫米)的软骨。我们从来不治疗这种缺陷，但如果我们一年后再看一次，这个10毫米的缺陷总是会自行愈合的。因此，这是另一个自然愈合的软骨缺陷的例子。因为我们制造了这个缺陷，然后可以跟踪它是如何随着时间的推移愈合的，所以它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疗法患者作为自然软骨愈合的人体实验模型。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)、膝关节手术期间对关节本身的视觉检查、显微镜下检查修复组织的活组织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，在哪里形成新的软骨细胞是活跃的，有多少新的软骨和骨已经形成，如果新的组织填满了整个受损的区域，软骨的表面有多光滑，以及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。除了我们的细胞治疗患者，所有的缺陷都会愈合，我们还将研究一组有软骨缺陷的韧带重建患者。其中只有一半能愈合，所以我们可以比较这两组人，也许还能更多地了解是什么控制了自然软骨的愈合。

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.