The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study

Abstract

Background: There is a need to improve therapies for osteoarthritis in horses.

Objectives: To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses.

Study design: Randomised, double-blinded, placebo-controlled experiment.

Methods: In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically.

Results: No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group.

Main limitations: This study assessed the short-term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error.

Conclusions: Equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses. The Summary is available in Spanish - see Supporting Information.

Keywords: allogeneic; horse; metacarpophalangeal joint; model; peripheral blood.

Figure 1

A schematic presentation of the adhered time line with an overview of the different procedures performed at each time point.

Figure 2

The evolution of the a) American Association of Equine Practitioners (AAEP) lameness scores and b) the response to flexion scores over the entire study period of 11 weeks for the horses treated with the placebo control product (CP) and the investigational veterinary product (IVP). The number of horses per score category is displayed per time point of evaluation. W, week. *Significant difference between the two treatment groups for that time point of evaluation with P<0.05.

Figure 3

The evolution of the mean vector sums (+s.e.) measured with the inertial sensor‐based system at the different time point of evaluation on a) treadmill, b) left circle, c) straight line before flexion and d) straight line after flexion. W, week. CP, control product. IVP, investigational veterinary product. *Significant difference between the two treatment groups for that time point of evaluation with P<0.05. The black horizontal bar indicates the threshold for lameness (i.e. 8.5 mm).

Figure 4

The evolution of the a) the joint effusion scores and b) the synovial fluid viscosity scores over the entire study period of 11 weeks for the placebo control product (CP)‐treated horses and the investigational veterinary product (IVP)‐treated horses. The number of horses per score category is displayed per time point of evaluation. W, week; d, day. *Significant difference between the two treatment groups for that time point of evaluation with P<0.05.

Figure 5

a) A representative example at gross examination of the proximal surface of the first phalanx of a horse treated with the placebo control product (CP) and a horse treated with the investigational veterinary product (IVP) (Week 11). Full thickness wear lines (indicated with the black arrows) are visible in the CP‐treated joint, but not in the IVP joint. Synovial hyperaemia (indicated with the white arrow) was also more pronounced in the CP‐treated joint compared with the IVP‐treated joint. In both joints, the dorsomedial osteochondral (OC) fragment, which was still attached to the joint capsule, was clearly visible (encircled). b) The mean area percentages (+s.e.) of glycosaminoglycans (GAGs), cartilage oligomeric matrix protein (COMP) and collagen type II as seen during histological and immunohistochemical analysis of the articular cartilage sampled adjacent to the OC fragment and at the level of the groove lesion of the CP‐ and IVP‐treated horses and of the equivalent areas in the healthy sham operated joints. *Significant difference between the treatment groups with P<0.05.