Abstract
BackgroundIntra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. The objective of this study was to assess the clinical response to repeated intra-articular injection of allogeneic versus autologous MSCs prepared in a way to minimize xeno-contaminants in a large animal model.MethodsIntra-articular injections of bone marrow-derived, culture-expanded MSCs to a forelimb metacarpophalangeal joint were performed at week 0 and week 4 (six autologous; six autologous with xeno-contamination; six allogeneic). In the week following each injection, clinical and synovial cytology evaluations were performed.ResultsFollowing the first intra-articular injection, there were no differences in clinical parameters over time. Following the second intra-articular injection, there was a significant adverse response of the joint to allogeneic MSCs and autologous MSCs with xeno-contamination with elevated synovial total nucleated cell counts. There was also significantly increased pain from joints injected with autologous MSCs with xeno-contamination.ConclusionsRepeated intra-articular injection of allogeneic MSCs results in an adverse clinical response, suggesting there is immune recognition of allogeneic MSCs upon a second exposure.
Highlights
Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy
We demonstrated that intra-articular injection of autologous MSCs without efforts to minimize bovine protein contamination resulted in markedly increased adverse clinical reaction
In strong contrast to previous reports [17, 18] a single intra-articular injection of autologous MSCs did not result in an adverse clinical reaction and there were no increases in total nucleated cell count (TNCC), joint effusion or pain [17, 18]
Summary
Intra-articular injection of mesenchymal stem cells (MSCs) is efficacious in osteoarthritis therapy. A direct comparison of the response of the synovial joint to intra-articular injection of autologous versus allogeneic MSCs has not been performed. There have been no reports directly comparing the clinical response to intra-articular injection of autologous and allogeneic MSCs other than those in the equine model, where a lack of clinically relevant differences have been reported [17, 18]. In each of these experimental reports, moderate to marked adverse clinical reaction with pain and joint effusion with cellular infiltrates were reported after a single intra-articular injection of autologous or allogeneic MSCs [17, 18]. There are no reports on the response to repeated intra-articular injection of autologous or allogeneic MSCs in any species
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