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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0503-8) contains supplementary material, which is available to authorized users.

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These results provide an insight into the success of medical management for presumptive thoracolumbar disk herniation in dogs and may allow for refinement of treatment protocols.

Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation.

We compared the relative sensitivity of computed tomography (CT) and myelography for identification of disk herniation in dogs. Criteria for patient selection included presurgical CT, myelography, or both and surgical or necropsy confirmation of disk herniation between the T3 and L6 vertebral articulations. Imaging findings were described as positive or inconclusive. Adverse events such as hypotension, cardiac arrhythmias, seizures, death, and lower urinary tract infection were compared between imaging groups. One hundred and eighty-two dogs met the inclusion criteria, with 116 dogs having myelography performed as the initial diagnostic imaging modality and 66 dogs having CT performed as the initial modality. The relative sensitivity for locating the site of disk herniation was 83.6% when myelography was the first test performed and 81.8% when CT was the first test performed. CT was more sensitive than myelography at detecting lesions in chronically affected dogs (P ¼ 0.025). Myelography was more sensitive than CT at detecting lesions in smaller dogs (o5 kg; P ¼ 0.004). Dogs that received both imaging modalities were significantly more likely to die or be euthanized compared with myelography alone (Po0.001). Both myelography and CT are reasonable diagnostic imaging modalities for locating the site of disk herniation. CT should be considered especially in heavier, more chronically affected dogs. The major limitations of this study include lack of randomization to imaging modality and the use of surgical exploration or necropsy as the gold standard.