Vetnews | Mei 2024 16 « BACK TO CONTENTS Allogeneic Mesenchymal Stem Cells: a step into the future for patients with degenerative osteoarthritis Marianne Lomberg BVSc Hons With improvements in health care and nutrition, our companion animals are living longer. Unfortunately, that also means degenerative conditions such as osteoarthritis are being diagnosed at an increasing rate in dogs, cats and horses. When inflammation goes bad: the molecular basis of degenerative osteoarthritis Degenerative joint disease is a physiological condition as much as a mechanical one. Macroscopically, it is the wearing away of intraarticular cartilage at a rate higher than the body’s ability to repair it. Physiologically, though, the process is more complex. The breakdown of cells causes the release of pro-inflammatory cytokines and other catabolic mediators in the joint. The purpose: to attract cells which can clean up the damaged tissue, revascularise and build new tissue to replace it. In a discrete, acute injury, this works perfectly. However, in animals with chronically unstable joints, the ongoing damage occurs faster than the body can repair it. The result is an ongoing inflammatory cytokine response which causes a continuous catabolic state and with it, chronic pain. (Sutton et al, 2009) Rebalancing the inflammatory response Interventions for degenerative osteoarthritis are aimed at either reducing the speed of breakdown or increasing the speed of regeneration, to the point where balance is restored. This can be done in four ways: 1) Reducing the inflammatory response through medication or dietary anti-inflammatory supplementation slows the catabolic process. However, in highly catabolic states or very unstable, far-progressed joints, these alone are insufficient to ensure the return to quality of life for patients. 2) Reducing mechanical pressure on the affected joints through surgery, weight management or exercises aimed at strengthening the surrounding muscles. This reduces the cause of joint wear, but it doesn’t correct the molecular process and therefore may not be sufficient for returning quality of life. 3) Placing an inert barrier between the nerve-containing tissues in affected joints. Intra-articular installations of viscoprosthetic agents such as polyacrylamide (Noltrex™, distributed in SA by V-Tech), provide this mechanical pain relief and can be life-saving in patients where owner finances or patient age do not allow corrective interventions, but the fact that a viscous, infiltrative foreign body is being permanently placed in a joint reduces its desirability in younger animals. 4) Encouraging tissue repair. In the past, this was achieved by placing the building blocks of the damaged cells into the body and relying on existing cells to use them appropriately – think dietary glucosamine supplementation or hyaluronic acid injections - or by focusing the body’s repair response on the damaged tissue – the principle used in Platelet Rich Plasma treatments. Recently, veterinarians have been able to add stem cell therapy to the regenerative modalities used. What makes stem cells different from other regenerative modalities? In fact, every treatment modality aimed at increasing the rate of tissue repair relies on stem cells. • In Platelet Rich Plasma (PRP) administration, the aim is to degranulate platelets before administration. This causes the release of chemotactic agents which attract leukocytes (to clear up the damaged tissue fragments) and haematopoietic progenitor cells – stem cells primed to become blood vessels. So PRP is essentially a way of directing the body’s stem cells towards treated areas. • Autologous Stromal Vascular Fraction (SVF) administration, goes one step further. When using this method, practitioners harvest mesenchymal fat. The fat is prepared with the aim of isolating and concentrating the stem cells. SVF administration delivers stem cells directly to the area where they’re needed. However, preparation is costly and time-consuming, and it is impossible to verify how many viable stem cells are being administered. • This is why Allogeneic Mesenchymal Stem Cells have become the most desirable tool for enhancing the physiological process of tissue regeneration. After harvesting visceral fat, the cells are not simply isolated and concentrated as with SVF, but then cultured (encouraged to multiply). In the process, Major Histocompatibility Complex (MHC) type II surface markers which identify cells as originating from a different host animal, are also removed. This means that stem cells from one donor can be used in a different patient – making allogeneic mesenchymal stem cells (MSCs) an off-the-shelf solution.
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