A Randomised, Double-Blinded, Placebo Controlled Proof-of-Concept Study Evaluating Equine Chondrogenic-Induced Mesenchymal Stem Cells as a Treatment for Osteoarthritis
Presented by: Charlotte Beerts
Authors: C. Beerts1, S. Y. Broeckx1,2, A. M. Martens2, A. L. Bertone3, L. Van Brantegem4, L. Duchateau5, L. Van Hecke1, M. Dumoulin2, M. Oosterlinck2, K. Chiers4, H. Hussein3, F. Pille2 and J. H. Spaas1
Affiliations: 1Global Stem cell Technology NV, Anacura group, Evergem, Belgium firstname.lastname@example.org; email@example.com; firstname.lastname@example.org; email@example.com 2 Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium firstname.lastname@example.org; email@example.com; firstname.lastname@example.org; email@example.com ; firstname.lastname@example.org 3 Department of Veterinary Clinical Sciences, Ohio State University, Columbus, USA email@example.com; firstname.lastname@example.org 4 Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium email@example.com; firstname.lastname@example.org 5 Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium email@example.com
Introduction: Osteoartritis (OA) is a major cause of early retirement in leisure and sport horses. The current conservative treatments are focused on pain relieve and do not stop progression of the disease, let alone reverse it. Over the past years, the use of regenerative treatments for degenerative joint lesions have gained an increasing interest. Several authors described promising results following an intra-articular injection with native mesenchymal stem cells (MSCs), however only limited cartilage repair was observed. Furthermore, different studies reported the combined use of chondrogenic-induced allogeneic MSCs and plasma with very favorable results. Nevertheless, randomized, double-blinded, placebo-controlled studies were still lacking.
Hypothesis / Objectives: Therefore, the goal of this study was to evaluate the efficacy of a single intra-articular injection of a combination of equine peripheral blood-derived allogeneic chondrogenic-induced MSCs and equine allogeneic plasma compared with physiological serum in an experimental model of metacarpophalangeal OA.
Materials and Methods: OA was induced in 12 healthy horses using a surgical experimental model. Five weeks later, horses were randomly allocated to 2 treatment groups: an intra-articular injection with either chondrogenic-induced mesenchymal stem cells in combination with equine allogeneic plasma (investigational veterinary product (IVP)), or physiological serum (placebo control). During the course of the study, a weekly joint and lameness assessment was performed (Figure 1). Arthrocentesis was performed to collect synovial fluid for cytology and biomarker examination at different time points. The horses were euthanized on week 11 and a macroscopic and histologic evaluation of metacarpophalangeal joints was done.
Results: No serious adverse events or suspected adverse drug reactions were observed. The lameness was significantly reduced in the treatment group (P=0.002; Figure 2). Joint effusion was significantly decreased in the IVP group (Figure 2). A significantly higher synovial fluid viscosity (P=0.02 and P=0.006; Figure 2) and lower glycosaminoglycan concentration was observed in the IVP group (P=0.004). The post mortem examination revealed significantly less wear lines and synovial hyperaemia in the IVP group (P=0.02 and P=0.01; Figure 3). The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans was significantly higher in cartilage of the IVP group (Figure 3).
Conclusions: Based on these results, the combination of equine allogeneic chondrogenic-induced MSCs and EAP seems to be a promising treatment for OA in horses. However, since this study reports the evaluation of the treatment with an experimental model of OA in a limited number of horses, further research is necessary on a large number of horses with naturally occurring OA.
Acknowledgements, Funding, and Conflicts of Interest: This research was funded by a grant (number 130543) from Vlaio and by Global Stem cell Technology (GST). The author JHS declares competing financial interests as shareholder in Global Stem cell Technology (GST) NV. SYB, JHS, CB and LVH are all employed by GST. SYB and JHS are inventors of several pending patents owned by GST (BE2012/0656; WO2014053418A9; WO2014053420A1; PCT/EP2013/075782). The other authors declare no conflicts of interests. The content of this manuscript contains the product Arti-Cell® Forte owned by GST.