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Treatment of tendon disease with multipotent mesenchymal stromal cells (MSC) is a promising option to improve tissue regeneration. To elucidate the mechanisms by which MSC support regeneration, longitudinal tracking of MSC labelled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) could provide important insight. Nine equine patients suffering from tendon disease were treated with SPIO-labelled or nonlabelled allogeneic umbilical cord-derived MSC by local injection. Labelling of MSC was confirmed by microscopy and MRI. All animals were subjected to clinical, ultrasonographical, and low-field MRI examinations before and directly after MSC application as well as 2, 4, and 8 weeks after MSC application. Hypointense artefacts with characteristically low signal intensity were identified at the site of injection of SPIO-MSC in T1- and T2∗-weighted gradient echo MRI sequences. They were visible in all 7 cases treated with SPIO-MSC directly after injection, but not in the control cases treated with nonlabelled MSC. Furthermore, hypointense artefacts remained traceable within the damaged tendon tissue during the whole follow-up period in 5 out of 7 cases. Tendon healing could be monitored at the same time. Clinical and ultrasonographical findings as well as T2-weighted MRI series indicated a gradual improvement of tendon function and structure.

Tendon disease has been treated with multipotent mesenchymal stromal cells (MSCs) in the equine large-animal model with promising success. The aim of this study was to gain more insight into the fate and biodistribution of MSCs after local application into tendon lesions by long-term cell tracking in this large-animal model. Superficial digital flexor tendon lesions were induced in all limbs in six horses and injected with 10106 Molday ION Rhodamine B-labeled MSCs suspended in serum or serum alone. Follow-up was performed using low-field magnetic resonance imaging (MRI), flow cytometry, and histology. Cell tracking based on the hypointense artifacts induced by the superparamagnetic iron oxide (SPIO) labeling agent in MRI as well as based on Rhodamine B fluorescence was feasible. However, Prussian blue staining for assessment of histology was not entirely specific for SPIO. Labeled cells could be traced at their injection site by MRI as well as histology for the whole follow-up period of 24 weeks. Although the numbers of labeled cells within the injected tendon lesions decreased over time, part of the applied cells appeared to remain viable and integrated within the injured tissue. Furthermore, small numbers of labeled cells were identified in peripheral blood within the first 24 h after cell injection and could also be found until week 24 within the contralateral control tendon lesions that had been injected with serum. The present findings unveil details on MSC biodistribution and persistence after their local application, which are of clinical relevance with regard to MSC safety and mechanisms of action.

SummaryReasons for performing study: Reductions in distances between dorsal spinous processes on radiographs are used as criteria for the diagnosis of impingement of the thoracic dorsal spinous processes in horses but are potentially altered by spine motion and different head and neck positions. Objectives: To determine the influence of head and neck positions on intervertebral distances between dorsal spinous processes on radiographs of thoracic spines of clinically sound horses. Methods: Lateral-lateral radiographs were obtained from 23 horses in 3 head and neck positions. The width of the thoracic dorsal spinous processes and intervertebral distances between adjacent thoracic dorsal spinous processes were measured at points perpendicular to a tangent between the dorsal spinous processes and the caudal extremity of the thoracic vertebrae. Results: A low head and neck position increased intervertebral distances between adjacent thoracic dorsal spinous processes from the 8th to 15th dorsal spinous processes whereas a high head and neck position had the opposite effect (P<0.05). Overall, intervertebral distances between adjacent thoracic dorsal spinous processes decreased from cranial to caudal in intermediate head and neck positions (P<0.01). The 12th thoracic dorsal spinous process was readily identifiable due to its significant difference to the narrower cranial and broader caudal dorsal spinous process (P<0.05). Conclusions:The head and neck position influences the distances between the dorsal spinous processes of the vertebrae of equine thoracic spine on radiography. Potential relevance: The measuring system reported here offers potential to improve and standardise radiographic evaluation of thoracic dorsal spinous processes.

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