title: Long-Term Cell Tracking Following Local Injection of Mesenchymal Stromal Cells in the Equine Model of Induced Tendon Disease.
abstract: 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.
authors.forename: Janina
authors.initials: J
authors.lastname: Burk
authors.forename: Dagmar
authors.initials: D
authors.lastname: Berner
authors.forename: Walter
authors.initials: W
authors.lastname: Brehm
authors.forename: Aline
authors.initials: A
authors.lastname: Hillmann
authors.forename: Carolin
authors.initials: C
authors.lastname: Horstmeier
authors.forename: Christoph
authors.initials: C
authors.lastname: Josten
authors.forename: Felicitas
authors.initials: F
authors.lastname: Paebst
authors.forename: Giacomo
authors.initials: G
authors.lastname: Rossi
authors.forename: Susanna
authors.initials: S
authors.lastname: Schubert
authors.forename: Annette B
authors.initials: AB
authors.lastname: Ahrberg
mesh_terms: D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005434:Flow Cytometry; D006736:Horses; D008279:Magnetic Resonance Imaging; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D012235:Rhodamines / Q000737:chemistry; D013708:Tendon Injuries / Q000601:surgery / Q000628:therapy*; D013710:Tendons / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005290:Ferric Compounds; D012235:Rhodamines; C000499:ferric oxide; C029773:rhodamine B