Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations

Abstract

The recent interest in advanced biologic therapies in veterinary medicine has opened up opportunities for new treatment modalities with considerable clinical potential. Studies with mesenchymal stromal cells (MSCs) from animal species have focused on in vitro characterization (mostly following protocols developed for human application), experimental testing in controlled studies and clinical use in veterinary patients. The ability of MSCs to interact with the inflammatory environment through immunomodulatory and paracrine mechanisms makes them a good candidate for treatment of inflammatory musculoskeletal conditions in canine species. Analysis of existing data shows promising results in the treatment of canine hip dysplasia, osteoarthritis and rupture of the cranial cruciate ligament in both sport and companion animals. Despite the absence of clear regulatory frameworks for veterinary advanced therapy medicinal products, there has been an increase in the number of commercial cell-based products that are available for clinical applications, and currently the commercial use of veterinary MSC products has outpaced basic research on characterization of the cell product. In the absence of quality standards for MSCs for use in canine patients, their safety, clinical efficacy and production standards are uncertain, leading to a risk of poor product consistency. To deliver high-quality MSC products for veterinary use in the future, there are critical issues that need to be addressed. By translating standards and strategies applied in human MSC manufacturing to products for veterinary use, in a collaborative effort between stem cell scientists and veterinary researchers and surgeons, we hope to facilitate the development of quality standards. We point out critical issues that need to be addressed, including a much higher level of attention to cell characterization, manufacturing standards and release criteria. We provide a set of recommendations that will contribute to the standardization of cell manufacturing methods and better quality assurance.

Clinical applications of adipose-derived stromal vascular fraction in veterinary practice

“… 2021 ; Ivanovska et al. 2022 ). In addition, regenerative medicine involving cellular therapy is increasingly used as a common mode of treating osteoarthritis (Gugjoo, Chandra et al.…”

“…Osteoarthritis is a chronic joint disease that occurs secondarily to developmental orthopaedic diseases such as hip/elbow dysplasia, cranial cruciate ligament disease, and patellar dislocation (Ivanovska et al. 2022 ). Secondary osteoarthritis is the common type of osteoarthritis seen in dogs.…”

Efficacy of autologous mesenchymal stromal cell treatment for chronic degenerative musculoskeletal conditions in dogs: A retrospective study

“…Immunophenotyping was carried out based on the methods described by Krešić et al ( 60) and Ivanovska et al (61). Briefly, seven cell lines of MSCs (taken at random from the bank of MSCs stored at the lab) were cultured to passage 2 and when 80% confluent were trypsinised as described above.…”

“…The MSCs used here were autologous adipose derived MSCs, culture expanded using standardized protocols, release criteria and strict quality control in a cell culture laboratory authorized by the Veterinary Medicines Directorate, thus complying with the Position Statement (53). Additionally, subsequent recommendations by Ivanovska et al in the manufacturing of MSCs for the treatment of OA in canine patients were also met (61). MSCs differentiated into chondrocytes and osteocytes but not into adipocytes, despite being derived from adipose tissue.…”

“…This is important for veterinary treatments and also confirms the potential for translational applications in human medicine. Both Ivanovska et al and Webb et al have advocated the use of naturally occurring canine disease, treated with standardized RM protocols, as an important area of research to bridge the gap between in vitro studies and human clinical trials (61,80).…”