Long-Term Safety and Efficacy of Single or Repeated Intra-Articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells for Managing Pain and Lameness in Moderate to Severe Canine Osteoarthritis Without Anti-inflammatory Pharmacological Support: Pilot Clinical Study.

Quentin Cabon,Véronique Livet,Eric Viguier,Marine Febre,Nadia Plantier,Rodolphe Rakic,Claude Carozzo,Nathalie Saulnier,Clément Robert,Thibaut Cachon,Philippe Saas,Stéphane Maddens,Niels Gomez,Paul Pillard

doi:10.3389/fvets.2019.00010

Abstract

Objective: To explore the long-term safety and efficacy of canine allogeneic mesenchymal stromal cells (MSC) administered intra-articularly as single or repeated injections in appendicular joints of dogs affected by moderate to severe refractory osteoarthritis.Study Design: 22 pet dogs were recruited into a non-randomized, open and monocentric study initially administering one cellular injection. A second injection was offered after 6 months to owners if the first injection did not produce expected results.Materials and Methods: Anti-inflammatory treatment (if prescribed) was discontinued at last one week before the onset of treatment. Each injection consisted of at least 10 million viable neonatal allogeneic mesenchymal stromal cells obtained from fetal adnexa. Medical data was collected from veterinary clinical evaluations of joints up to 6 months post-injection and owner's assessment of their dog's mobility and well-being followed for a further 2 years when possible.Results: Mild, immediate self-limiting inflammatory joint reactions were observed in 5/22 joints after the first injection, and in almost all dogs having a subsequent injection. No other MSC-related adverse medical events were reported, neither during the 6 months follow up visits, nor during the long-term (2-years) safety follow up. Veterinary clinical evaluation showed a significant and durable clinical improvement (up to 6 months) following MSC administration. Eight dogs (11 joints) were re-injected 6 months apart, sustaining clinical benefits up to 1 year. Owner's global satisfaction reached 75% at 2 years post-treatmentConclusion: Our data suggest that a single or repeated intra-articular administration of neonatal MSC in dogs with moderate to severe OA is a safe procedure and confer clinical benefits over a 24-month period. When humoral response against MSC is investigated by flow cytometry, a positive mild and transient signal was detected in only one dog from the studied cohort, this dog having had a positive clinical outcome.

Highlights

Osteoarthritis (OA) is the most common cause of lameness in dogs older than 1 year and accounts for 20% of all canine referrals [1]
Twenty-two pet dogs were enrolled over a 15-month period and were analyzed in a 2-year safety study with a 95% successful follow up rate
Dog#19 included for right hip was withdrawn after lameness and swelling of the right tarsus

Summary

Introduction

Osteoarthritis (OA) is the most common cause of lameness in dogs older than 1 year and accounts for 20% of all canine referrals [1]. Prevalence of age-related diseases such as OA have increased in parallel for dogs and their owners as a consequence largely of medical advances. This increase has been exacerbated by issues of being overweight and a more sedentary life style. Non-steroidal anti-inflammatory drug (NSAID) administration is still the cornerstone of mild to moderate OA pharmacological management. Their pharmacokinetic properties necessitate daily or at least repeated dosing over a long period, leading to adverse events that compromises their long-term use [2, 3]. Expensive surgical management of OA (i.e., arthrodesis, joint resection of the femoral or humeral head, osteotomy for angular correction) carries a significant risk of morbidity while prostheses are not available for all joints

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