Introduction

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for all orthopaedic disease. Small animal laboratory animals have been used extensively to test MSC use for the treatment of musculoskeletal disease and a great deal has been learned from cellular therapies from rodent models, but rodents are considered atomically inferior to equine models in their cartilage thickness, joint size, and joint forces. (1) Horses as athletes also provide a source of naturally occurring disease including articular cartilage trauma, osteoarthritis (OA), meniscal injury, and osteochondritis dissecans. Experimental studies using horses as a model for post traumatic osteoarthritis (PTOA) and focal articular cartilage defects provide multiple objective criteria for evaluation that include both symptom and disease modification

Content

Equine Post Traumatic Osteoarthritis Model (PTOA):
Equine in-vivo models of joint disease include PTOA and models for focal articular cartilage defects. A PTOA model has been well described in the middle carpal joint of horses. (2) This model, through the creation of bone and cartilage debris as well as an osteochondral fragment, results in secondary OA that mirrors clinical disease and can also be effectively monitored with radiographs. Of twenty published studies, one study compared the intraarticular injection of culture expanded bone marrow derived MSCs (BMSCs) compared to stromal vascular fraction (SVF). (3) Briefly, under general anesthesia, diagnostic arthroscopy using a lateral arthroscopic approach is performed on both middle capital joints. One previously randomized middle carpal joint has an 8-millimeter osteochondral fragment created on the distal dorsal aspect of the radial carpal bone and the defect in the parent bone was debrided back to a 15-millimeter width with the bone debris remaining in the joint. Two weeks after creation of the fragmentation, horses begin an exercise protocol of two-minute trot/ two-minute gallop/ two-minute trot emulating a normal treatment training regimen for a Thoroughbred racehorse. The study then goes out to day 70 from the time of induction and there are regular weekly examinations and clinical assessments with radiographs at the beginning and end of the study. Following euthanasia, macroscopic and microscopic assessments are done and the macroscopic and microscopic and a historic grading system for experimental models of OA cartilage degradation was used and this has been published. (4) BMSCs performed better in this model compared to SVF with regard to differences in inflammatory mediators. We have also published encouraging results for intra-articular BMSCs as a complementary therapy following femorotibial joint arthroscopic surgery for the treatment of meniscal disease, articular cartilage erosion, and OA. (5)

Equine Models of Focal Articular Cartilage Healing
A number of equine models of focal cartilage healing have been developed at both Colorado State University (CSU) and Cornell University, and these techniques have been summarized in a review paper in Cartilage (6). Multiple models in the femoropatellar and medial femorotibial joints have been used. The first model in the femorotibial articulation developed involves is a full thickness 1-cm² on the medial formal condyle (MFC) that is created arthroscopically and was designed to emulate a focal defect on the weight bearing portion of the human medial femoral condyle. With regard to progenitors cell studies, intra-articular injection of BMSCs were tested using this model. Twelve joints with MFC defects were microfractured and HA administered intra-articularly 4 weeks after lesion creation. This was compared to twelve other joints with MFC defects that were microfractured and injected intra-articularly with 20 million BMSCs plus HA four weeks after lesion creation. (7) The articular cartilage repair studies go out for 12 months normally as other studies have shown progress in healing over that time period. We also start treadmill exercise at 3 months and go through to 12 months and this was the protocol in this study. Arthroscopic examination was performed at four months and twelve months, at which time the study was terminated. There was a significant increase in firmness of repair tissue at four month and twelve-month arthroscopic examinations, as well as significantly increased aggrecan content in the repair tissue at 12 months. (7) A number of models have also been developed on the medial and lateral trochlear ridges of the femur within the femoropatellar articulation to test multiple cellular therapies including MSCs. One notable study was evaluation of the addition of MSCs to autologous platelet- enhanced fibrin scaffolds in chondral defects. (8) Full-thickness defects were created on the lateral trochlear ridge of the femur under arthroscopic guidance and then, using gas arthroscopy the platelet enhanced fibrin scaffold was placed into the defect in both groups. It was found that addition of BMSCs to autologous platelet advanced fibrin scaffolds in chondral defects was inferior to autologous platelet- enhanced fibrin scaffolds alone. (8) What was of greatest concern was that four out of ten of the of the BMSCs in fibrin/ PRP defects filled the majority of the defect with bone. This reflected some previous misgivings about the BMSCs for articular cartilage repair. That had previously been brought up by Charles Archer. Related to this, we also evaluated articular cartilage progenitor cells in the repair of articular defects in an equine model in fibrin in a collaborative project with Prof. Archer and had good results without any evidence of bone formation (9)

References

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