Alternative Equine Therapies

Alternative Therapies

Regenerative Therapies

The field of regenerative medicine is in a constant state of development. "Healing" is best described as a gradient of repair quality, with regeneration at the top of the scale and development of scar tissue at the bottom. Regenerative capacity refers to the ability of a tissue to renew, replace or repair itself to its original architecture, quality and function. Degeneration is the opposite: the progressive deterioration of structure and function. Unfortunately, most tissues' tendency is to repair themselves with scar tissue, or in the case of arthritis, to continue the degenerative process. The field of regenerative medicine is the study of methods used to get injured tissue to heal as closely to its original architecture as possible; in essence, seeking regeneration. Even after diligent rehabilitation horses with tendon and/or ligament injuries experience re-injury at rates ranging from 35% up to 70% for some of the more physically demanding disciplines (racing). The equine athlete is also prone to arthritis, which is irreversible once it starts. Rest and physical rehabilitation are the therapeutic standards, but advances in the field of regenerative medicine have added new implements to the veterinarian's toolbox. Interleukin-1 receptor antagonist protein (IRAP), platelet-rich plasma (PrP), bone marrow and stem cells are biologic technologies derived from the animal's own body that modulate the inflammatory and healing processes, bringing our horses closer to the ultimate goal of regeneration after injury. These are not instant cures and failure is often more related to unrealistic expectations than to the therapies themselves.


IRAP

Interleukin-1 is an inflammatory mediator that stimulates degenerative processes in the body. To act, this molecule (called a cytokine) must interact with a receptor, in essence switching on a pathway that releases damaging enzymes. Interleukin-1 receptor antagonist protein (IRAP) is another molecule that fits in that same receptor; however, instead of activating the process, it blocks it. By drawing the horse's blood and incubating it in a specialized collection system, this protein can be isolated and concentrated. It can then be injected into arthritic joints in an effort to block some of the major inflammatory pathways and stop the degenerative process. The principles behind the use of IRAP are well established in arthritis models, but not enough work has been done to prove definitive advantage in the treatment of tendon or ligament injuries. It is ready 24 hours after drawing the blood and is injected into the arthritic joint(s) once a week for 3-4 treatments, and often monthly thereafter. This treatment will not (nor will any other) reverse damage already done and is best used in the early stages of the disease process.


Platelet-Rich-Plasma (PRP)

Platelets are cell-like elements in the bloodstream that are classically associated with blood clot formation. They also contain tiny granules full of a multitude of growth factors that promote everything from cellular proliferation to angiogenesis (formation of new blood vessels) to epithelialization (covering of an open wound with healthy new skin). Centrifugation or specialized collection kits are used to concentrate the platelets into the horse's own plasma (the clear element of the blood) creating "platelet-rich plasma". Upon injection the platelets are activated and the granules open releasing the growth factors into the target tissue. These growth factors attract cells responsible for everything from matrix/tissue production to the cleanup of damaged tissue and cellular debris. The advantages of PrP include the diverse range of growth factors delivered, ease of production and potential for immediate use. The main disadvantage is that tendons and ligaments have very few innate cells and PrP does not provide an immediate source of cells. That said, it combines very well with the cellular therapies discussed below.

Stem Cell Therapy

Stem cell therapy has evolved rapidly as a treatment approach in veterinary medicine, particularly for addressing musculoskeletal injuries in athletic horses. Current technology enables us to take fat, skin, blood or, more commonly, bone marrow and, under special laboratory conditions, create stem cells. These cells are then implanted back into the same horse in areas of injury, where they will become the type of cell required to repair that injury.

Implantation is usually performed under sedation with ultrasound to guide the injection. This can be performed on an out-patient basis. The veterinary surgeon responsible for your horse will discuss the potential benefits and risks associated with stem cell therapy, together with post-implantation care and exercise. Complications are very rare.

Bone Marrow

Tendons and ligaments take so long to heal because they have so little blood supply and so few cells. They are almost entirely a collagenous extracellular matrix. Instead of relying on the few cells that are already there, bone marrow injection provides a source of cells for local repair. While bone marrow comprises many different cell types, our primary target is its stem cell population. Stem cells are undifferentiated cells isolated from fat or bone marrow, and can be injected into a lesion to provide an immediate source of cells for the healing process. Stem cells exist in a more primordial state than the rest of the body's cells. They have the unique ability to differentiate into (become) cells that produce almost any type of tissue in the body. Bone marrow-derived stem cells seem to have the greatest potential for tendon and ligament injuries because they are already "programmed" to become connective tissue-type cells. Bone marrow is harvested fairly easily from different sites in the body; most commonly the sternum and the point of the hip. Once obtained, it is either injected as is or is centrifuged in an effort to inject a smaller volume with a higher concentration of stem cells. A typical injection contains 10,000 - 100,000 cells. Importantly, centrifugation does not increase the actual number of cells being injected, just the concentration. While it has not been proven that more cells are necessarily better, most stem cell research showing measurable improvements in healing parameters has been done with cell numbers in the millions. The benefits (relative to culture-expended cells; see below) are the ability to obtain and inject the cells immediately and decreased cost. Clinical studies have reported success, but robust investigations comparing treated horses to a control group are lacking.


Culture-expanded stem cells

Instead of injecting bone marrow immediately after harvest, the cells obtained can be cultured over 2-3 weeks to expand their numbers. Cells are isolated and allowed to divide in a controlled laboratory setting, yielding final injection numbers in the millions. This pure population of cells can be re-suspended in other therapeutic agents, like PrP, for multi-faceted therapy. The advantages of this method are the sheer number of cells and the ability to combine that number of cells with other therapies. The disadvantages are the 2-3 week wait, two hospital visits and the higher cost. To avoid the wait, researchers are looking at banked and allogeneic stem cells. Foals' umbilical cords contain stem cells that can be harvested and expanded at birth, then banked for future use. Allogeneic cells are cells that come from a different animal of the same species (another horse). Having a separate source for cells has clear time, efficiency and cost advantages so work investigating the efficacy and safety of these options is underway.


Fat derived stem cells

Involves collection of subcutaneous fat from the croup region as a source of a wide variety of stemcells that are then extracted from the fat and returned for injection 2 days later.


Future

Many different pathways, degenerative, reparative and regenerative, are at work in these injuries. Research is investigating gene therapy and combinations in which multiple mediators are administered: those that stop degenerative pathways and those that boost regenerative pathways. Think genetically modified stem cells that not only produce tendon matrix, but also constantly express genes for growth factors and other modulatory proteins. Instead of a single injection, the very cells that populate the healing tissue will also produce growth factors. As amazing as these adjunctive therapies are, they are just that: adjunctive. The mainstays of treatment of any musculoskeletal disease, from arthritis to tendonitis, are appropriate modulation of activity and physical rehabilitation. While the basics remain the same, recent advances in regenerative medicine have increased our abilities to heal our horses and the future is just as exciting!