Safety and clinical efficacy of a single intra-articular injection of allogeneic neonatal mesenchymal stem cells for the treatment of osteoarthritis in dogs
[um_loggedin show_lock=yes]Authors: téphane Maddens1 (s.maddens@vetbiobank.com), Niels Gomez2 (nielsgomez1@gmail.com), Marine Febre1 (m.febre@vetbiobank.com), Thibaut Cachon2,3 (thibaut.cachon@vetagro-sup.fr), Nathalie Saulnier1 (n.saulnier@vetbiobank.com), Paul Pillard2 (paul.pillard@vetagro-sup.fr), Eric Viguier2,3 (eric.viguier@vetagro-sup.fr)
Affiliations: (1)Vetbiobank SAS, France (2)Small Animal Surgery, VetAgro Sup, France ; (3)UPSP 2016A104, ICE, Interaction cells environment, France
Introduction: As in human, prevalence of osteoarthritis (OA) is increasing in canine population, mainly in relationship with the ageing of the population. First line treatment to manage OA is based on non-steroidal anti-inflammatory drugs (NSAID), however, frequent dosing or long-term NSAID administration may induce severe side effects. New therapeutic approach, such as cell therapy with Mesenchymal Stem/stromal Cell (MSCs), is gaining increasing interest in the field of orthopedics for the treatment of chronic inflammatory diseases such as OA. MSCs, through their interaction with cellular microenvironment and through a secretion of a wide array of bioactive molecules may reduce inflammation and limit tissue degradation.
Hypothesis/Objectives: The objective of this study was to evaluate the effects of a single IA injection of allogeneic canine neonatal MSCs in dogs suffering from severe naturally-occurring OA.
Materials and Methods: MSCs were prescribed as a compassionate treatment in an open-label, uncontrolled study after other therapeutic approaches being excluded. Animals with confirmed hip, elbow or stifles OA were eligible with no restriction in weight, age, sex, or breed. Dogs enrolled in this study were injected intraarticularly with 10E7 neonatal MSCs, in 1 or 2 joints independently. Outcome measures were veterinary clinical evaluation by scoring at 1, 3, and 6 months post-injection, along with a global owner assessment of their dog’s wellness up to 2 years post-treatment. Furthermore, we evaluated a potential humoral response towards cellular product by measuring the presence of alloantibodies against MSC antigens or product contaminant like FCS
Results: Twenty-two client-owned dogs were recruited in the study among whose sixteen completed the study. Three dogs were dropped out from the study because of medical reasons and 3 dogs were withdrawn because of non-compliance of the follow up visits. No systemic adverse effect was observed after MSCs injection during the entire course of the study. Compared to baseline, clinical evaluation showed a significant improvement 1-month (p=0.02), 3 months (p = 0.0001) and 6 months (p=0.0088) post treatment. Long-term safety results collected from a survey completed by 13 owners reported no MSC-related adverse event during the two-year follow up. No MSC-antibodies were detected in dog’s serum following treatment
Conclusions: This study provides additional evidence for the long-lasting effect of allogeneic MSC therapy (up to 6 months) in alleviating pain and lameness in dogs with OA and a stabilization of OA progression over 2 years. The absence of detection of alloantibodies following IA injection of neonatal allogeneic MSCs suggests that this therapeutic approach is well-tolerated and could be repeated if required
Acknowledgements, Funding, and Conflicts of Interest: SM is a current shareholder of Vetbiobank. MF and NS were employed by Vetbiobank at the time of the study. There is no commercial or financial connection between Vetbiobank and the four co-authors (EV, TC, NG, PP).
Vetbiobank, FRANCE, partially funded the study by supplying graciously the cell product tested and covering clinical and imaging costs.[/um_loggedin]