eprintid: 20217 rev_number: 11 eprint_status: archive userid: 1589 dir: disk0/00/02/02/17 datestamp: 2016-03-01 08:16:39 lastmod: 2016-03-01 10:45:12 status_changed: 2016-03-01 08:16:39 type: article metadata_visibility: show creators_name: Geburek, Florian creators_name: Mundle, Kathrin creators_name: Conrad, Sabine creators_name: Hellige, Maren creators_name: Walliser, Ulrich creators_name: van Schie, Hans T. M. creators_name: van Weeren, René creators_name: Skutella, Thomas creators_name: Stadler, Peter M. title: Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions - a pilot study subjects: 570 divisions: 53100 abstract: Background: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Methods: Four adult warmblood horses received a unilateral injection of 10 × 106 autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. Results: AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Conclusions: Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 106 AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT. date: 2016 publisher: BioMed Central id_scheme: DOI id_number: http://dx.doi.org/10.1186/s13287-016-0281-8 ppn_swb: 165531274X own_urn: urn:nbn:de:bsz:16-heidok-202171 language: eng bibsort: GEBUREKFLOTRACKINGOF2016 full_text_status: public publication: Stem Cell Research & Therapy volume: 7 number: 21 place_of_pub: London pagerange: 1-12 issn: 1757-6512 citation: Geburek, Florian ; Mundle, Kathrin ; Conrad, Sabine ; Hellige, Maren ; Walliser, Ulrich ; van Schie, Hans T. M. ; van Weeren, René ; Skutella, Thomas ; Stadler, Peter M. (2016) Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions - a pilot study. Stem Cell Research & Therapy, 7 (21). pp. 1-12. ISSN 1757-6512 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/20217/1/13287_2016_Article_281.pdf