Regenerative Medicine and Orthobiologics

Regenerative medicine and orthobiologics are a hot topic in the world of equine medicine. As a potential new and improved option for joint disease and tendon/ligament injury, these treatments are getting a lot of attention in the sport horse world. No matter if your goal is to jump 1.60m at the Olympic Games or spend your weekends riding in the mountains, prevention and treatment of lameness is an essential part of general equine wellness. Two of the most common causes of lameness are joint disease or osteoarthritis and soft tissue injuries such as tendonitis (tendon inflammation) or desmitis (ligament inflammation). Traditional treatments for both of these general conditions have been aimed at halting inflammation but have lacked the ability to promote a healthier cellular environment. Regenerative medicine has potential applications in both of these areas.

Michele and Scorch at the Canadian Barrel Horse Association. Photo courtesy of Michele Pankiw

Regenerative medicine is defined as medicine that replaces or regenerates human or animal cells, tissues, or organs, to restore or establish normal function. Orthobiologics are a particular form of regenerative medicine that aims at treating musculoskeletal injuries including osteoarthritis and tendon/ligament injuries. Traditionally, regenerative medicine has focused on transplanting cells that had been prepared outside of the body into an inflamed or injured space in the hopes of stimulating healthy cell growth in that area but with no regard for the potential inflammatory environment of the tissue. New approaches try to work with the body, relying on a “soup” of anti-inflammatory proteins and growth factors to stimulate the body’s own regenerative mechanisms. This soup is often referred to as the secretome. Within this aim of trying to repair damaged tissue as opposed to just halting inflammation, orthobiologics show great promise in the realm of treating musculoskeletal injuries and even potentially preventing disease progression.

There are a wide range of orthobiologic products on the market that can generally be classified into 2 categories, autologous and allogenic. Autologous products are biologics that have been collected and processed for use on the individual itself. Allogenic products are biologics that have been collected from multiple individuals of the same species and then processed for use at a later date in a different individual. At present, the primary orthobiologics available for use on our equine patients are autologous, though allogenic products are a growing area and you may see more of these in the future.

At Burwash Equine Services, we have multiple types of regenerative medications available for treatment of our patients, each with its unique benefits and potential applications. A brief summary of each follows here:


Platelet Rich Plasma (PRP)

- Autologous blood product processed stall side in ~30 minutes for immediate use

- Blood is centrifuged to activate and concentrate platelets at 3-5X baseline

- Growth factors and proteins within PRP stimulate the body’s response of “healthy” inflammatory cells to area of tissue injury

o Increase formation of blood vessels, connective tissue, and epithelium

- Primary evidence for use in tendon or ligament injuries (e.g. administration via ultrasound guided injection into a tendon lesion)

o Improves blood supply and strength of tissue

o Earlier reduction of lameness

o Shorter rehabilitation times

o Decreased rates of re-injury

- Has some support for use to decrease inflammation in joint disease


IRAP (Autologous Conditioned Serum)

- IRAP = Interleukin receptor antagonist protein

o An important counter protein to the inflammatory cascade of joint disease

o Autologous conditioned serum (ACS) was primarily processed and researched to increase concentrations of the IRAP protein but is now known to also contain other anti- inflammatory proteins & growth factors

- Blood is collected and incubated with medical glass beads for 24 hours to stimulate the production of IRAP

o Serum is then collected and frozen for future use

o Typically results in 6-8 doses

- Primary evidence for use in joint disease in a series of 4 injections each 1 week apart

o Improves lameness and range of motion

o Improves parameters of joint health

o Short-term duration within joint fluid but long-term benefit to the joint

- Has some support for use in soft tissue disease (e.g. suspensory ligament desmitis)


Pro-Stride (Autologous Protein Solution)

- Neither a PRP nor an ACS but has a combination of properties from both

o Optimum concentration of platelet derived growth factors and anti-inflammatory proteins including IRAP

- Blood is pulled and processed stall-side within ~30 minutes for immediate use

- Use in tendon & ligament injury shows:

o Improved quality of healed tissue on a cellular level

o Earlier reduction in lesion size

o Improved elasticity of healed tendons

- Use in joint disease & osteoarthritis shows:

o Improved lameness and range of motion by 2 weeks and for up to 52 weeks

o Improved parameters of joint health

Prostride processing unit at Burwash Equine Services. Curious to see how it works? Check out our TikTok video at the bottom of this article.

Stem Cells

- Parent cells that have the ability to differentiate (change) into other cells

- In sports medicine, we typically rely on mesenchymal stem cells (MSCs) that can differentiate into bone, tendon, cartilage, and/or fat

o Most commonly obtained from bone marrow or adipose (fat) tissue

o Bone marrow derived MSCs have smaller initial cell concentrations but appear superior in their ability to differentiate into musculoskeletal tissue

- Previously thought to work via transplantation into injured tissue, but studies have shown poor long-term survival

o Instead, rely on enhanced “secretome” of growth factors and anti-inflammatory proteins from the MSCs that:

o Alters the body’s immune response,

o Reduces inflammation,

o Stimulate natural tissue regeneration

o Ultimate goal is to produce tissue that closely resembles original tissue

- Cultured & Expanded MSCs

o Most commonly, stem cells are harvested from the sternum or pelvis in hospital and then sent to a lab for culture and expansion

o Typically spend 2-4 weeks in a lab

o Expanded sample contains high concentrations of stem cells for administration by veterinarian to injured area

- Bone Marrow Aspirate Centrate

o MSCs obtained from the bone marrow can be processed stall side for same day use

o Benefit in immediacy of treatment but generally lower concentration of stem cells compared to cultured & expanded stem cells

o Some evidence that higher concentrations of MSCs are required for improved tissue repair in tendon/ligament injury

- Primary evidence for use of stem cells is in tendon/ligament injury

o Can be administered via ultrasound guided injection into a lesion or into a vein or artery for a general tissue perfusion

o Improved strength & elasticity of repaired tissue with better blood supply and less fibrosis. Repaired tissue is more similar to parent tissue

o Significantly decreased rates of re-injury

- Also some evidence for use in joint disease with improved lameness and joint health parameters

Treatment comparison chart. Courtesy of Dr. Katy White

In general, regenerative medications such as those listed above provide veterinarians with an exciting new tool box of potential treatments to help keep our horses performing their best. Potential benefits of regenerative medication include:

- Potential to repair and/or prevent joint inflammation

- Potential for improved healing of soft tissue injuries

- Potential for greater anti-inflammatory effect than steroids

- Less chance of cartilage toxicity than certain steroids

- Decreased risk of laminitis for metabolic horses compared to steroids

- Generally considered safe for use in horses

Further, while we have focused primarily on applications for musculoskeletal disease, there are many other potential applications within equine medicine including treatment of laminitis, infection, wound repair, surgery, reproduction, and ophthalmology, amongst others. While an exciting and growing area of veterinary medicine, it is important not to get caught up in the hype. There are lots of new products coming out and your veterinary team at Burwash Equine Services is here to help you decide which treatments are best suited to your horse with the most evidence for use and practicality of treatment.

Reach out today for an appointment if you are interested in learning more!


References:

1. Ribitsch, I., Oreff, G. L., & Jenner, F. (2021). Regenerative medicine for equine musculoskeletal

diseases. Animals, 11(1), 234.

2. Gugjoo, M. B., & Sharma, G. T. (2019). Equine mesenchymal stem cells: properties, sources,

characterization, and potential therapeutic applications. Journal of equine veterinary science,

72, 16-27.

3. Ortved, K. F. (2018). Regenerative medicine and rehabilitation for tendinous and ligamentous

injuries in sport horses. Veterinary Clinics: Equine Practice, 34(2), 359-373.

4. Velloso Alvarez, A., Boone, L. H., Pondugula, S. R., Caldwell, F., & Wooldridge, A. A. (2020).

Effects of autologous conditioned serum, autologous protein solution, and triamcinolone on

inflammatory and catabolic gene expression in equine cartilage and synovial explants treated

with IL-1β in Co-culture. Frontiers in Veterinary Science, 7, 323.

5. White, G. F., Gómez Álvarez, C. B., & Lewis, R. (2021). Are biologics more effective than corticosteroids for

intra‐articular treatment of osteoarthritis?. Equine Veterinary Education, 33(7), 389-392.