BackgroundOsteochondral injuries represent a significant clinical problem requiring novel cell-based therapies to restore function of the damaged joint with the use of mesenchymal stromal cells (MSCs) leading research efforts. Pre-clinical studies are fundamental in translating such therapies; however, technologies to minimally invasively assess in vivo cell fate are currently limited. We investigate the potential of a MRI- (magnetic resonance imaging) and superparamagnetic iron oxide nanoparticle (SPION)-based technique to monitor cellular bio-distribution in an ovine osteochondral model of acute and chronic injuries.MethodsMSCs were isolated, expanded and labelled with Nanomag, a 250-nm SPION, and using a novel cell-penetrating technique, glycosaminoglycan-binding enhanced transduction (GET). MRI visibility thresholds, cellular toxicity and differentiation potential post-labelling were assessed in vitro. A single osteochondral defect was created in the medial femoral condyle in the left knee joint of each sheep with the contralateral joint serving as the control. Cells, either GET-Nanomag labelled or unlabelled, were delivered 1 week or 4.5 weeks later. Sheep were sacrificed 7 days post implantation and immediately MR imaged using a 0.2-T MRI scanner and validated on a 3-T MRI scanner prior to histological evaluation.ResultsMRI data demonstrated a significant increase in MRI contrast as a result of GET-Nanomag labelling whilst cell viability, proliferation and differentiation capabilities were not affected. MRI results revealed evidence of implanted cells within the synovial joint of the injured leg of the chronic model only with no signs of cell localisation to the defect site in either model. This was validated histologically determining the location of implanted cells in the synovium. Evidence of engulfment of Nanomag-labelled cells by leukocytes is observed in the injured legs of the chronic model only. Finally, serum c-reactive protein (CRP) levels were measured by ELISA with no obvious increase in CRP levels observed as a result of P21-8R:Nanomag delivery.ConclusionThis study has the potential to be a powerful translational tool with great implications in the clinical translation of stem cell-based therapies. Further, we have demonstrated the ability to obtain information linked to key biological events occurring post implantation, essential in designing therapies and selecting pre-clinical models.

Objective The aim of this study was to assess computed tomography (CT) images of cadaveric feline stifles and record the relationship between the patella and femoral trochlea in normal stifles; then to investigate the effect of block recession trochleoplasty (BRT) with and without partial parasagittal patellectomy (PPP) on patellofemoral contact, depth of patellar recession and size of trochlea and patella. Materials and Methods The sample population included six cat cadavers (12 stifles). Preoperative CT scans with stifles in three positions: extended (155–165°), neutral (85–95°) and flexed (35–45°). Lateral stifle arthrotomy was followed by BRT. CT scans were taken as above. PPP was performed so the width of the patella was 1 mm narrower than the BRT. CT scans were repeated and CT measurements were taken. Results The area of contact between the patella and femoral trochlea was significantly reduced after BRT and then significantly increased after PPP. The depth of patellar recession was unchanged after BRT, but then was significantly higher after PPP. The patella was wider than the trochlea preoperatively and post-BRT and narrower post-PPP. Reduction in bone volume following PPP (mean: 20%) was 50% the reduction in patella width (mean: 40%). Conclusion Block recession trochleoplasty did not improve patellar recession and decreased patellofemoral contact area. Following BRT, the patella rides the trochlear ridges and loses contact with the trochlear sulcus. Block recession trochleoplasty alone should not be performed in cats. Instead, BRT should be combined with PPP.

Many potential treatments for orthopedic disease fail at the animal to human translational hurdle. One reason for this failure is that the majority of pre‐clinical outcome measurements emphasize structural changes, such as gross morphology and histology, and do not address pain or its alleviation, which is a key component of treatment success in man. With increasing emphasis on “patient reported outcome measurements (PROM)” in clinical practice, in this study we have used two different telemetric methods (geolocation and Fitbark activity trackers, Kansas City, MO) to measure movement behavior, i.e., an indirect PROM, in an ovine osteoarthritis induction and an osteochondral defect model performed in adult female Welsh Mountain sheep. This study demonstrates that both systems can be used to track movement and activity of experimental sheep before and after surgery and that the Geolocator system recorded a decrease in distance moved and activity at the end of the experimental period in both models. The Fitbark activity tracker also recorded significant alterations in movement behavior at the end of these studies and this method of recording showed a correlation between Fitbark data and radiography, macroscopic and histological scoring (well recognized outcome measurements), particularly in animals with large (10 mm) defects, i.e., more severe pathology. These results suggest that telemetry is able to track movement behavior in experimental sheep and that the methodology should be considered for inclusion in outcome measures in preclinical orthopedic research. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:1498–1507, 2018.

TitleFunctional characterization of ovine dorsal root ganglion neurons reveal peripheral sensitization after osteochondral defect.