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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

Geburek, Florian ; Mundle, Kathrin ; Conrad, Sabine ; Hellige, Maren ; Walliser, Ulrich ; van Schie, Hans T. M. ; van Weeren, René ; Skutella, Thomas ; Stadler, Peter M.

In: Stem Cell Research & Therapy, 7 (2016), Nr. 21. pp. 1-12. ISSN 1757-6512

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Download (3MB) | Lizenz: Creative Commons LizenzvertragTracking 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 by Geburek, Florian ; Mundle, Kathrin ; Conrad, Sabine ; Hellige, Maren ; Walliser, Ulrich ; van Schie, Hans T. M. ; van Weeren, René ; Skutella, Thomas ; Stadler, Peter M. underlies the terms of Creative Commons Attribution 3.0 Germany

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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.

Item Type: Article
Journal or Publication Title: Stem Cell Research & Therapy
Volume: 7
Number: 21
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 01 Mar 2016 08:16
Date: 2016
ISSN: 1757-6512
Page Range: pp. 1-12
Faculties / Institutes: Medizinische Fakultät Heidelberg > Institut für Anatomie und Zellbiologie
Subjects: 570 Life sciences
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