Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know

Abstract

Biological cell-based therapies for the treatment of joint disease in veterinary patients include autologous-conditioned serum, platelet-rich plasma, and expanded or non-expanded mesenchymal stem cell products. This narrative review outlines the processing and known mechanism of action of these therapies and reviews current preclinical and clinical efficacy in joint disease in the context of the processing type and study design. The significance of variation for biological activity and consequently regulatory approval is also discussed. There is significant variation in study outcomes for canine and equine cell-based products derived from whole blood or stem cell sources such as adipose and bone marrow. Variation can be attributed to altering bio-composition due to factors including preparation technique and source. In addition, study design factors like selection of cases with early vs. late stage osteoarthritis (OA), or with intra-articular soft tissue injury, influence outcome variation. In this under-regulated field, variation raises concerns for product safety, consistency, and efficacy. Cell-based therapies used for OA meet the Food and Drug Administration's (FDA's) definition of a drug; however, researchers must consider their approach to veterinary cell-based research to meet future regulatory demands. This review explains the USA's FDA guidelines as an example pathway for cell-based therapies to demonstrate safety, effectiveness, and manufacturing consistency. An understanding of the variation in production consistency, effectiveness, and regulatory concerns is essential for practitioners and researchers to determine what products are indicated for the treatment of joint disease and tactics to improve the quality of future research.

Keywords: Food and Drug Administration regulation; autologous conditioned plasma; autologous-conditioned serum; cell-based therapies; mesenchymal stem cells; osteoarthritis; platelet-rich plasma.

Figure 1

Summary of the production process for mesenchymal stem cells (MSCs). At each stage in the production process (top), specific factors may influence the yield, viability, and/or behavior of MSCs in veterinary patients. These factors need to be considered during clinical use of MSCs and controlled for, or described, in preclinical and clinical research.

Figure 2

Schematic of the source and distribution of cytokines and growth factors in blood-derived cell-based products. Cytokines and growth factors are derived from leukocytes and platelets, respectively. All blood-derived cell-based products have a combination of cytokines and growth factors, which vary in amount depending on how the products are produced. Leukocytes and platelets can be concentrated by centrifugation or filtration techniques or, the cytokines and growth factors are released during the production process, e.g., by interaction with borosilicate glass and during clot formation.

Figure 3

Outline of clinical and laboratory parameters that can be standardized or recorded to enhance interpretation of clinical trial results for cell-based therapy. Standardization and recording for cell-based therapies will be imperative in regulatory approval pathways.