Ex vivo MRI cell tracking of autologous mesenchymal stromal cells in an ovine osteochondral defect model

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Markides, H, Newell, KJ, Rudorf, H, Ferreras, LB, Dixon, JE, Morris, RH ORCID: https://orcid.org/0000-0001-5511-3457, Graves, M, Kaggie, J, Henson, F and El Haj, AJ, 2019. Ex vivo MRI cell tracking of autologous mesenchymal stromal cells in an ovine osteochondral defect model. Stem Cell Research & Therapy, 10 (1): 25. ISSN 1757-6512

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Official URL: http://doi.org/10.1186/s13287-018-1123-7

Abstract

Background: Osteochondral 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.

Methods: MSCs 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.

Results: MRI 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.

Conclusion: This 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.

Item Type:	Journal article
Publication Title:	Stem Cell Research & Therapy
Creators:	Markides, H., Newell, K.J., Rudorf, H., Ferreras, L.B., Dixon, J.E., Morris, R.H., Graves, M., Kaggie, J., Henson, F. and El Haj, A.J.
Publisher:	BioMed Central
Date:	2019
Volume:	10
Number:	1
ISSN:	1757-6512
Identifiers:	Number Type 10.1186/s13287-018-1123-7 DOI 1123 Publisher Item Identifier
Rights:	This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	14 Jan 2019 11:59
Last Modified:	14 Jan 2019 11:59
URI:	https://irep.ntu.ac.uk/id/eprint/35546