Magnetic resonance imaging of iron oxide labelled stem cells: Applications to tissue engineering based regeneration of the intervertebral disc

Abstract

Minimally-invasive monitoring of regeneration in diseased tissue is an important aspect of stem cell therapy. Magnetic resonance imaging (MRI) based tracking of cells labelled with ferumoxides has the potential for non-invasive in vivo detection and longitudinal assessment of implanted cells. Cells labelled with ferumoxides appear as hypointense regions on MR images and thus can be distinguished from the surroundings. Application of this methodology to intervertebral disc degeneration (IVD), and detection of labelled cells implanted into the disc for tissue regeneration was examined. Mesenchymal stem cells labelled with a ferumoxide contrast agent were imaged in vitro to quantitatively characterize the signal intensity loss using MRI relaxation parameters (T 1 , T 2 , and T 2 *). To determine whether labelled cells could be detected within scaffolds suitable for implantation, labelled cells were seeded within both natural and synthetic polymers and imaged using MRI. Labelled cells were loaded within poly(ethylene glycol) hydrogels and imaged in vitro using both MRI and confocal microscopy. Labelled cells were also loaded into fibrin gels, and detected ex vivo within rat IVDs using MRI. Lastly, the effect of ferumoxide labelling on cell viability was investigated. Quantitatively, labelled cells demonstrate the greatest signal intensity loss and contrast on T 2 *-weighted images. Labelled cells can be detected in both synthetic and natural polymers, and can be distinguished from the native tissue environment of the rat IVD. Finally, labelling does not significantly impair cell viability. Consequently, this technique shows promise as a potential method for in vivo longitudinal tracking of stem cell based regeneration of the IVD.

Construction of a tissue engineered intervertebral disc with high biological activity using an allogeneic intervertebral disc supplemented with transfected nucleus pulposus cells expressing exogenous dopamine beta-hydroxylase

“…However, the existing available artificial material is not able to meet the requirements for tissue engineered intervertebral discs in either biocompatibility or strength (Lumpkins et al, 2008;Nesti et al, 2008;Lumpkins and McFetridge, 2009). The problems of connection force and sealability have not yet been solved in the techniques currently used for connecting the artificial fibrous ring and the artificial upper and lower end-plates (Saldanha et al, 2008;Foss et al, 2013). In contrast, the allogeneic frozen intervertebral disc used in the present experiment is able to completely meet the above three conditions as the support material for the tissue engineered intervertebral disc.…”

Mesenchymal stem cell tracking in the intervertebral disc

“…Coated with dextran and PEG and combined with protamine sulfate, USPIONs have been cultured with human Adipose Derived Stem Cells (hADSCs) within a three dimensional scaffold [96] . In vitro, no effect on cell viablilty or osteogenic differentiation was seen from cell from unlabeled cells on T1 weighted imaging [105] . This group also demonstrated SPION labeled cells, loaded in a fibrin gel and injected via fluoroscopic guidance, could be identified ex vivo within the IVD of excised rat tails [105] .…”

“…In vitro, no effect on cell viablilty or osteogenic differentiation was seen from cell from unlabeled cells on T1 weighted imaging [105] . This group also demonstrated SPION labeled cells, loaded in a fibrin gel and injected via fluoroscopic guidance, could be identified ex vivo within the IVD of excised rat tails [105] . Further research by Prologo et al [62] imaged MSCs labeled with a radioactive marker (iodine-124 2'fluoro-2'-deoxy-1β-D-arabinofuranosyl-5-iodouracil) using CT and PET.…”

“…Saldanha et al [105] demonstrated feasibility by imaging MSCs labeled with SPION (Feridex ® ) in vitro to quantitatively characterize signal intensity loss using T1, T2 and T2* relaxation parameters. T2* weighted gradient echo (GRE) images demonstrated the most significant loss of signal intensity from labeled cells.…”

“…Ongoing effective research will facilitate the translation of MSC treatment for IVD disease to clinical practice. [105] , 2008…”