Orthobiologics in Equine Practice: What’s Available and What Do We Know?

In Part 1 of VetPD’s Untangling Orthobiologics in Equine Practice masterclass, Kyla Ortved, DVM, PhD, DACVS, DACVSMR, from the University of Pennsylvania, reviewed the current evidence supporting stem cells, autologous blood-based products, and amnion therapies for horses. Her presentation focused on how clinicians can use existing data to make more informed treatment decisions while recognizing the limitations that still exist within the field.

Horses are elite athletes frequently affected by musculoskeletal injury. As such, said Ortved, orthobiologics are most commonly used in the treatment of joint disease and soft tissue injury, including osteoarthritis (OA), meniscal injuries, and tendon and ligament injuries, especially affecting the deep and superficial digital flexor tendons.

Ortved explained that underlying many of these conditions is inflammation, which drives tissue degeneration while simultaneously impairing healing. Orthobiologics aim to modulate this inflammatory environment, improve tissue repair quality, and reduce reinjury rates, she said. However, she cautioned against unrealistic expectations.

“Regenerative medicine has great capabilities to change the immune response, improve quality of repair tissue, and decrease reinjury rates, but it does not decrease the need for appropriate rehabilitation and does not decrease the speed to return to high intensity work. Our goal is to have a better end product.”

Stem Cells

Ortved explained that stem cells must possess both self-renewal capacity and potency, or the ability to differentiate into other cell types. While pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells (iPSCs) have broad differentiation potential, most clinically relevant equine therapies involve multipotent mesenchymal stem cells (MSCs).

MSCs are particularly attractive in orthopedic medicine because they can differentiate into tissues such as cartilage, tendon, adipose tissue, and muscle. However, Ortved explained that the current understanding of MSCs has shifted from earlier assumptions.

“When they first came on the scene, everyone was extremely excited about it because of the potency of cells,” she said. “You would put them in the place of injury, and they would just make new tissue.”

Instead, MSCs appear to function primarily through immunomodulation and paracrine signaling. “They modulate the local tissue by secreting signals, cytokines, growth factors into their environment and, fortunately for us, these effects are further increased in inflamed environments,” she explained.

Sources of MSCs include bone marrow, adipose tissue, umbilical cord blood and tissue, and amniotic membrane. Of these, bone marrow and adipose tissue remain the most practical adult sources.

“Bone marrow-derived MSCs tend to outperform adipose-derived MSCs in the musculoskeletal healing space,” she added.

Clinicians can use stem cells either immediately after collection—such as bone marrow aspirate concentrate (BMAC)—or after laboratory expansion to generate higher cell numbers over several weeks.

Stem Cells for Soft Tissue Injury. The strongest evidence supporting MSC use currently exists for tendon and ligament injury. Ultrasound-guided intralesional injection remains the primary delivery method, although regional limb perfusion has also shown promise in select cases.

Ortved noted that multiple studies have demonstrated improved clinical outcomes and lower reinjury rates in horses with SDFT injuries treated with bone-marrow-derived MSCs.

“MSCs for soft tissue injuries, especially in superficial digital flexor tendon injuries, has by far the most clinical research,” she said.

Ortved also discussed encouraging evidence for MSC use in meniscal injuries within the stifle. Studies evaluating postoperative MSC injections after arthroscopically confirmed meniscal lesions demonstrated improved outcomes compared with historical controls.

Stem Cells for Joint Disease. Evidence supporting MSC therapy for OA is more limited but continues to expand. Experimental and clinical studies suggest MSCs might improve cartilage healing and slow OA progression.

Ortved also reviewed growing interest in allogeneic stem cell products. These off-the-shelf therapies offer several advantages, including standardization, availability, and the ability to manipulate cells toward specific therapeutic functions, such as tenogenic or chondrogenic differentiation.

However, unlike in some species, equine MSCs are not truly immune privileged.

“These cells are recognized by the host immune system as foreign and can elicit that immune response that leads to cell death,” she cautioned.

While this might affect efficacy more than safety, it remains an important consideration when performing repeated dosing.

Several allogeneic products available in Europe have shown encouraging results, said Ortved. Tenogenic primed stem cell products such as RenuTend demonstrated improved return-to-work rates and lower reinjury rates in tendon injuries. Chondrogenically induced products such as Arti-Cell Forte have shown benefits in experimental OA models.

Ortved also highlighted a Canadian study evaluating umbilical-cord-tissue-derived MSCs in naturally occurring OA. Horses receiving MSCs plus hyaluronic acid demonstrated improved lameness scores and higher return-to-work rates compared to horses treated with hyaluronic acid alone.

Autologous Blood-Based Products

The second major category Ortved reviewed included platelet-rich plasma (PRP), autologous conditioned serum (ACS/IRAP), autologous protein solution (APS/Pro-Stride), and alpha-2 macroglobulin (A2M).

Platelet-Rich Plasma (PRP). Ortved emphasized that PRP remains highly variable between systems and preparations. By definition, PRP is plasma containing platelet concentrations above baseline whole blood values. Platelets contain numerous growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-β), which might support healing.

PRP preparations can be leukocyte-rich or leukocyte-poor, and the literature remains inconclusive regarding superiority between the two, said Ortved. Leukocyte-rich PRP, while containing higher concentrations of potentially inflammatory white blood cells, also contains high concentrations of interleukin-1 receptor antagonist (IL-1RA), which has potent anti-inflammatory benefits. Leukocyte-poor PRP may be preferable in acutely inflamed tissues where additional inflammatory stimulation is undesirable.

Evidence supporting the use of PRP is strongest for tendon injuries. Studies have demonstrated improved histologic appearance, biomechanical properties, lameness reduction, and ultrasonographic healing in SDFT lesions.

Evidence for OA treatment is more limited in horses, although systematic reviews suggest PRP likely improves lameness and clinical performance in equine OA patients.

Ortved also discussed emerging antimicrobial applications for PRP-derived products. BIO-PLY (Qentoros), an allogeneic PRP lysate enriched for antimicrobial peptides, demonstrated significant bacterial clearance and reduced pain scores in an experimental septic arthritis model.

ACS (IRAP). Autologous conditioned serum, commonly referred to as IRAP, is generated by stimulating leukocytes to produce anti-inflammatory cytokines, particularly IL-1RA.

Traditional ACS systems required 24-hour incubation periods, but newer point-of-care systems now achieve similarly high IL-1RA concentrations without incubation.

Evidence for ACS in soft tissue injury remains limited, though some studies report improved ultrasonographic and histologic healing. More substantial evidence exists for OA treatment, said Ortved, particularly following the landmark CSU carpal chip model study that established the commonly used protocol of four injections administered seven days apart.

APS (Pro-Stride). Ortved described APS as essentially a combination of ACS and PRP. APS contains concentrated platelets, activated leukocytes, high IL-1RA concentrations, soluble TNF receptor, TGF-β1, and high levels of A2M.

Studies evaluating APS for OA have shown improvements in lameness scores and force plate analysis following a single injection in horses with naturally occurring disease. Experimental synovitis studies also demonstrated improved gross and histologic synovial appearance following treatment.

Interestingly, said Ortved, APS processing appears to alter leukocyte populations toward more anti-inflammatory macrophage phenotypes, which may contribute to therapeutic effects.

Alpha-2 Macroglobulin (A2M). A2M is a protease inhibitor capable of inhibiting collagenases and aggrecanases involved in cartilage and tendon degradation.

Although commercial products such as Alpha-2EQ aim to concentrate A2M, Ortved noted that her group’s research found APS consistently contained higher A2M concentrations than the dedicated A2M product.

At present, equine clinical evidence for A2M remains lacking, she said, though rodent studies suggest potential benefits for tendon and cartilage healing.

Amnion-Based Therapies

Finally, Ortved reviewed amnion-derived products, which are processed into injectable particulate or liquid allografts. These therapies contain growth factors, cytokines, extracellular matrix proteins, and structural scaffolding components.

Amnion products are thought to possess anti-inflammatory, antifibrotic, and proregenerative properties, though published evidence remains limited.

One multicenter study involving 100 horses with soft tissue injuries reported that 72 horses returned to work after treatment with an amnion allograft product, while an additional 10 horses returned to work at a lower level.

Takeaways

Ortved concluded by emphasizing that while orthobiologic therapies remain promising, clinicians must critically evaluate the evidence supporting each product.

She encouraged veterinarians to carefully consider what a product actually contains, whether it has demonstrated efficacy, and whether available evidence supports its use.

“I think our current preclinical and clinical data is quite promising, especially in naturally occurring disease,” she said, “But there’s always a need for more randomized, placebo-controlled, double-blind clinical trials.”

Visit VetPD.com to register for the Untangling Orthobiologics in Equine Practice masterclass in its entirety, which runs through July 7.

Related Reading

• Platelet-Rich Plasma for Equine Joint Therapy: Where Are We At?
• Disease Du Jour: Diagnosing and Managing Equine Soft Tissue Injuries
• Autologous Conditioned Serum/IRAP—Help or Hype?

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