Ultra Short Echo Time MRI of Iron-Labelled Mesenchymal Stem Cells in an Ovine Osteochondral Defect Model

Joshua D Kaggie,James Mackay,Gavin Houston,Fiona Gilbert,Alicia El Haj,Martin J Graves,Hareklea Markides,Frances Henson

doi:10.1038/s41598-020-64423-4

Abstract

Multipotent Mesenchymal Stem/Stromal Cells (MSCs) are widely used in cellular therapy for joint repair. However, the use of MSC therapies is complicated by a lack of understanding of the behaviour of cells and repair within the joint. Current methods of MSC tracking include labelling the cells with Super Paramagnetic Iron Oxide nanoparticles (SPIOs). However, standard acquisition sequences (T2 and T2*) give poor anatomical definition in the presence of SPIOs. To avoid anatomical compromise in the presence of SPIOs, we have investigated the use of Ultra-short Echo Time (UTE) MRI, using a 3D cones acquisition trajectory. This method was used to track SPIO labelled MSC injected into joints containing osteochondral defects in experimental sheep. This study demonstrates that multiple echo times from UTE with 3 T MRI can provide excellent anatomical detail of osteochondral defects and demonstrate similar features to histology. This work also monitors the location of SPIO-labelled cells for regenerative medicine of the knee with MRI, histology, and Prussian blue staining. With these methods, we show that the SPIOs do not hone to the site of defect but instead aggregate in the location of injection, which suggests that any repair mechanism with this disease model must trigger a secondary process.

Highlights

Osteoarthritis (OA) is the most common disease affecting the synovial joints
Both histology and Prussian Blue staining confirmed the presence of Super Paramagnetic Iron Oxide nanoparticles (SPIOs) in the fat pad and surrounding synovial fluid, where there was significant Magnetic Resonance Imaging (MRI) signal decay
The aim of this study was to demonstrate the utility of a novel MRI method for imaging SPIO-labelled Mesenchymal Stem/Stromal Cells (MSCs) and their subsequent effects in an ovine osteoarthritic model represented by joint defects

Summary

Introduction

Osteoarthritis (OA) is the most common disease affecting the synovial joints. OA causes significant welfare and economic burden in both animal and human healthcare[1]. New strategies for tissue engineering may be able to influence joint surface defect healing[2,3,4,5,6,7,8,9,10] These strategies include cell based therapies and small molecular treatments, which have been widely used in regenerative medicine[2,3,4,5,6,7,8,9,10]. Irrespective of the mechanism of action of MSC, there is a significant body of research that demonstrates the efficacy of MSC in treating such joint pathology as meniscal regeneration[18] and osteoarthritis[19,20] These results indicate that intra-articular MSC injections could represent a genuine therapeutic strategy for joint disease. The aim of this study was to evaluate the use of 3D cones MRI sequences for SPIO detection and for visualizing subsequent joint changes after the introduction of SPIO-labelled MSCs in an experimentally created osteochondral defect in a large animal preclinical model

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Conclusion