Author(s): Sarah Broeckx 1, Marieke Zimmerman 2, Sara Crocetti 3, Marc Suls 2, Tom Mariën 4, Stephen J. Ferguson 3,5, Koen Chiers 6, Luc Duchateau 7, Alfredo Franco-Obregón 3,5,8, Karin Wuertz 3,5,*, Jan H. Spaas 1,*
Degenerative joint disease (DJD) is a major cause of reduced athletic function and retirement in equine performers -. Medical treatment for DJD may include anti-inflammatory and analgesic drugs to reduce inflammation and pain, and so-called disease-modifying drugs such as glucosamine, chondroitin sulphate or hyaluronic acid -. In the case of severe cartilage and bone degeneration, the use of articular cartilage curettage, osteophyte removal or even arthrodesis could be suitable , . Nevertheless, the aforementioned therapies are merely aimed at alleviating the symptoms or enhancing clinical recovery, without inducing an actual regeneration of the affected joint.
The field of equine regenerative medicine is drawing increasing attention in the scientific community for its treatment strategies of joint pathologies. Equine mesenchymal stem cells (MSCs) are of specific therapeutic interest as they can differentiate in vitro towards cells with a hyaline-like cartilage morphology and produce cartilage-specific components such as collagen type II and glycosaminoglycans -. Moreover, horses may serve as a valuable large animal model for the evaluation of new human therapies concerning in vivo efficiency and safety, due to interspecies similarities in tendon structure ,  as well as thickness of the non-calcified cartilage of the stifle joint . Therefore, the evaluation of new treatments for musculoskeletal injuries in horses may be of broad clinical benefit for both equine and human medicine.
Other than a single case report with a positive clinical outcome of naturally occurring DJD after MSC therapy , the few available placebo-controlled studies in horses consist of experimentally induced cartilage lesions -, not entirely resembling the clinically observed pathology. Importantly, the micro-environment - or niche - in degenerated cartilage might not provide the correct signals for MSC differentiation or alternatively, may even negatively influence their viability. Therefore, a priori chondrogenic induction of MSCs may improve the clinical outcome. In fact, this approach of provoking tenogenic induction has been used in the past to treat different equine tendon lesions, with promising clinical results , . Therefore, a principal aim of this study was to evaluate the clinical effects of a combined therapy for the treatment of equine DJD, using either native MSCs plus platelet-rich plasma (PRP) or chondrogenic induced MSCs plus PRP. This approach was compared to the more conventional regenerative therapies based on the use of PRP or native MSCs alone, which have been shown to be clinically safe -. This study also sought to compare the therapeutic efficacies of chondrogenically-induced MSCs (plus PRP) to native MSCs (plus PRP).
Allogenic peripheral blood (PB) from one donor horse was used as the source of MSCs, since it has been previously reported that PB MSCs also have the capacity to produce cartilage in vitro , . Moreover, the same donor horse could be used to produce PRP, thus substantially increasing the standardization of the sample production and...