A toothbrush for the knee28 December 2023
In many cases, severe knee osteoarthritis is treated at an advanced age through replacing the knee joint. But prior to this point there’s very little in the way of treatment, and with cases of osteoarthritis increasing among younger patients, many must live with pain, discomfort and at times limited mobility for years before they can undergo joint replacement surgery. Mesenchymal stem cells have been touted as a potential treatment before the disease reaches this point, but extracting, culturing and delivering them to patients comes with its own challenges. Dennis McGonagle, professor of investigative rheumatology at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, is part of a team that invented a device to try and overcome these challenges and make the treatment more viable for patients. He speaks to Mae Losasso to explain how it works.
Hear the phrase ‘paradigm-shifting medical device’ and you’ll probably picture some nifty gizmo worthy of science fiction. Micro-implantables, say, or neuro-prosthetics or anti-gravity bio-printers. In 1966, only Bones McCoy, resident doctor on Star Trek’s Enterprise, could have had such gadgets at his disposal.
Today, however, these devices really do exist or at least are in the process of being designed, tested and patented. There’s reason enough to marvel at these modern medical devices, but we shouldn’t lose sight of the fact that such innovations are only ever as good as the science they serve. In other words, all that glitters may not be gold (or silicone or graphene or any other novel tech material).
Innovators may be good generating hype around a shiny new gadget, but all too often medical devices get rolled out before anyone can say just what their application might be. By the same token, not all pioneering medical devices need to be complicated, state-of-the-art contraptions. In many cases, the principle of Occam’s razor holds true; simplicity and efficacy go hand in hand. One recent invention, the STEM-device developed by rheumatology experts Thomas G. Baboolal, Elena Jones and Dennis McGonagle at the Leeds Institute of Rheumatic and Musculoskeletal Medicine is a case in point. “We called it a synovial brush, or a toothbrush for the knee,” McGonagle says. This no-frills bit of kit is a prime example of purposebuilt equipment, specifically designed to turn sound scientific theory into groundbreaking therapeutic reality. The handheld STEM-device might look like a toothbrush, but it’s what it does that matters.
Baboolal, Jones and McGonagle’s STEM-device is the product of almost two decades of research into native osteoarthritic abnormal joint environment and the mesenchymal stem cells (MSCs) that reside in synovial fluid. “We first discovered synovial fluid resident stem cells in 2004,” McGonagle explains. “And then in 2008, we found that these cells were 100 times more numerous in the fluid in early osteoarthritis.” Appearing in joint cavities, synovial fluid primarily works to lubricate and nourish articular cartilage. But when Jones and McGonagle discovered increased numbers of MSCs in the osteoarthritic abnormal joint environment, they began asking serious questions about where these cells originate and what they might do. In 2016, with Baboolal and others, they published their early findings in the Annals of the Rheumatic Diseases. Using a dog model of joint distraction – a technique whereby metal pins are placed across the knee joint to encourage space between the bones – McGonagle et al. demonstrated that “when we took out these stem cells, tagged them, re-injected them into the joint and pulled the joint apart, there was increased adhesion of these stem cells to the injured superficial cartilage,” he explains. “When you correct the mechanical environment,” so their theory goes, “the earliest pathology in osteoarthritis starts in the superficial cartilage and in the knee”.
Conservation, preservation and restoration
According to McGonagle, to date there are no proven medical therapies for osteoarthritis. The only established treatment is joint replacement, which, though tried and tested in a limited number of joints, is far from ideal. “For me, it’s like this,” McGonagle continues, “100 years ago you had dentists and they pulled teeth, and you had orthopaedic surgeons and they replaced joints. Now in dentistry, the last thing you want to do is pull a tooth: it’s all about conservation, preservation and restoration. The same is true in orthopaedic surgery. We know so much now about the reparative environment of osteoarthritis, that we could be getting all these [patients] in their 40s and 50s and creating an environment to regenerate the joints and keep them going without getting to this end-stage disease.”
It’s this vision that put McGonagle, Jones and Baboolal on a track to create the STEM-device. The team at Leeds are not the first to harness MSCs for osteoarthritis, but the brilliance of their approach lies in its sheer simplicity, economy and efficacy. “To repair cartilage”, McGonagle explains, “surgeons have used a number of methods with limited success, including bone microfracture, cartilage biopsy with digestion, and culture expansion with cell reintroduction in a scaffold”. In the latter procedure, stem cells derived from bone marrow and other sources are “expanded in an expensive facility for up to a month, and then injected back into the defect via a carrier,” says McGonagle. Using the STEM-device, however, this process might be radically simplified. In a recent
“One-hundred years ago you had dentists and they pulled teeth, and you had orthopaedic surgeons and they replaced joints. Now in dentistry, the last thing you want to do is pull a tooth: it’s all about conservation, preservation and restoration. The same is true in orthopaedic surgery.”
paper published by Dr Ala Altaie, a stem cell biologist working alongside the Leeds orthopaedic team, findings revealed that the synovial brush could release enough stem cells to make cartilage in the lab, without the need for culture expansion.
The STEM-device is designed to be used in conjunction with nascent regenerative orthopaedic procedures, such as joint distractions and wedge osteotomies. “We’re trying to set the scene so that surgeons appreciate that joints can repair themselves when you correct the environment,” McGonagle says. “When the surgeons are in the joint repairing it, they’re doing it under arthroscopy and irrigation, so the joint is expanded, and they are actually washing out stem cells and growth factors. What we’re saying is, if you give the synovium a good brushing at the end of the procedure, you’re effectively doing an orthopaedic rain dance. Swallows will find their way to Africa if you let them out of a cage in August, you don’t have to tag them; likewise, as we demonstrated in the lab, fluid stem cells will migrate into clots and find their way to sites of injury.”
A simple tool
The concept is promising, the device and procedure simple and affordable, and yet the reality so far has proved challenging. Back in 2014, while the device was still in its early stages of development, the team at Leeds lost Stuart Calder, one of its most enthusiastic members, in a tragic coastal accident. “That knocked us back,” McGonagle shares. Five years later, the team were preparing to conduct their first nationwide study, led by Hemant Pandit, professor of orthopaedic surgery at the University of Leeds and consultant orthopaedic surgeon at Leeds Teaching Hospitals’ NHS Trust. Looking at knee joint distraction as a means of spontaneously repairing cartilage, the study would put the synovial brush to the test – but research was stymied by the onset of the Covid-19 pandemic. As McGonagle explains, “12 centres in the UK were involved, but only Leeds recruited. Our limited data is now undergoing analysis.”
Despite these setbacks, the device itself continued to undergo a series of iterative tests. Once the team were happy with the shape, size and material of their synovial brush, the device was patented and then sold to Yorkshire-based medtech solutions company XIROS. Uptake, however, has been slow. In part, McGonagle suggests, this may be because the brush is devoid of high-tech bells and whistles. “The device is very simple, and it’s handheld,” he says. “One of the things [we] realised in hindsight is that surgeons like gadgets. A device that was battery operated and that spontaneously spun and rotated would be more attractive.” McGonagle’s comment might sound flippant, but the fact remains: many in the field expect more pizzazz from contemporary medical devices. Yet, as McGonagle stresses, the device remains merely a means to end.
Using what we’ve got
While the team at Leeds are confident that their synovial brush is the best tool for the job, they’re also prepared to consider the possibility that existing surgical implements might produce the same outcome – albeit with more abrasive effect and with greater risk of tissue loss. Ultimately, “there is a mindset that needs to change” McGonagle admits. “Even without our device, if surgeons appreciated this they could, in theory, use other [tools] for scraping and preparing surfaces in order to rough up the synovium.”
Will we see a STEM-device 2.0, something with more tech appeal? That’s certainly an option, McGonagle says, but the key message remains paramount: “Joints do repair from the top down with the stem cells in the fluid that comes from the synovium, and augmentation of that process in the context of proper mechanical alignment is likely to be very beneficial.”
The work of McGonagle et al. signals an exciting development in the field of osteoarthritic therapy, and one that could have widespread and lasting impact – if surgeons could only be persuaded to start adopting the device under procedural conditions. Of course, there remains work to be done to turn this theory into a reality as more trials and further studies will need to be carried out before we can be sure of the efficacy of this approach. But one thing that seems certain, our expectations about medical technology need to change. Putting the cart before the horse may work in other tech environments, but when it comes to medical science, the right tool for the job might just be as simple as a toothbrush.