The use of MRI and MNP to image and track cells in vivo for arthritic cell-based therapies

Abstract

Cell-based therapies have been proposed as novel approaches to treating Osteoarthritis and Rheumatoid Arthritis. A non-invasive means of monitoring cell populations, post implantation could prove valuable in the clinical translation of such therapies. We propose the use of superparamagnetic iron oxide nanoparticles (SPIONs; internalised by cell populations) with magnetic resonance imaging (MRI) to image and track cell populations in vivo.

We investigate the potential of commercially available SPIONs (SiMAG, Lumirem, Nanomag and P904) as potential labelling/tracking agents for in vivo investigations. Human mesenchymal stem cells (hMSC) and porcine chondrocytes were labelled with SPIONs under passive incubation conditions in either serum free media or serum containing media (24 hrs). SiMAG (10 µgFe/ml) demonstrated greatest potential with highest comparative internalised Fe content (labelled in serum free media) in vitro. SPION-labelled cell population maintained viability and proliferative capacity apart from SiMAG-labelled chondrocytes (10 µgFe/ml). Furthermore, SiMAG-labelled hMSC populations demonstrated successful differentiation down mesodermal lineages and retained key cell surface markers.

MRI visibility thresholds were investigated (in vitro and ex vivo). Dose dependant contrast was generated only by SiMAG-labelled populations in vitro when MR imaged. In vitro minimum visibility of SiMAG-labelled populations was influenced by various ex vivo tissues with similar contrast developing in muscle and fat tissue samples but not for ligament. Finally, an ex vivo model of articular cartilage damage confirmed the potential clinical application of SPIONS as cell tracking agents at optimised conditions (cell dosage and SiMAG concentration) using a clinical system.

An AIA murine model (Rheumatoid Arthritis) and a MNX rat model (Osteoarthritis) were implemented to image and track implanted SiMAG-labelled MSCs (murine) in vivo for 7 and 29 days, respectively. Additionally, clinically relevant functional outcomes were also monitored. Relevant in vitro assessment was performed where mMSCs efficiently internalised SiMAG with no impairment on cell activity. Good contrast was generated in both studies with SiMAG-labelled cell population located within the synovial cavity after 7 days (mouse study) and 29 days (rat study) by MRI. Administration of MSCs significantly reduced joint swelling in the mouse study without influence from the presence of SiMAG. mMSCs significantly influenced weight bearing asymmetry with little influence on paw withdraw threshold indicating potential antinocieotive properties of MSCs. In summary, SiMAG has demonstrated great potential as a labelling and tracking agent to be implemented for imaging and tracking cell populations.