Background: To detect and track super paramagnetic iron oxide nanoparticles (SPIONs) labelled human mesenchymal stem cells (hMSCs) in vivo during the course of antigen induced arthritis (AIA) rat model.
Methods: hMSCs were cultured and labelled in vitro using 0.2 mg Fe/ml SPIONs for 24 hours and non-labelled hMSCs were used as a control. After verifying hMSCs SPION labelling and cell viability, 500 000 SPION-labelled and control hMSCs as well as 9 μg SPIONs were injected intra-articularly (i.a.) on day 2 post-AIA induction. The animals were scanned on days 3, 6 and 10 using Siemens 3T clinical scanner with a 4 cm loop coil. The following MR sequences were used: T2 STIR, VIBE and UTE to visualise oedema, SPIONs and SPIONs as a positive contrast respectively. At the end of the experiment the animals were sacrificed, the knees isolated and processed for histology. The sections were Prussian blue stained for SPION visualisation and immunostained for CD44 as a hMSC marker consecutively.
Results: A strong SPION signal was detected on MR images 24 hours after the i.a. injection of SPION labelled hMSCs on both VIBE and T2 STIR sequences and could be detected up to day 10. This signal significantly changed between the different timepoints and its evolution pattern was different from that of SPIONs alone. No signal was found when non-labelled hMSCs or vehicle alone were injected. Furthermore, the signal caused by SPIONs alone had a specific distribution in the synovium which was significantly different from that of the SPION-labelled hMSCs. Co-localisation of Prussian blue particles and CD44 positive cells on histological sections confirmed a persisting uptake of the SPIONs by hMSCs.
Conclusion: Our findings show the feasibility of in vivo tracking of SPION labelled hMSCs in AIA. This protocol can be used to assess the outcome of regenerative therapy in arthritis.
Disclosure: The authors declared no competing interests. The research leading to these results has received funding from the European Union Seventh Framework Programme NMP-2008-4.0-1, GRANT AGREEMENT No 228929 (Project NanoDiaRA).