Imaging transplanted stem cells in real time using an MRI dual-contrast method

Abstract

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Enhancing regenerative approaches with nanoparticles

“…Alternative design strategies could help to overcome these limitations. For example, SPIO nanoparticles with gadolinium-based chelates (GdDTPA) allowed dual labelling of hMSCs, where live cells could be discriminated from dead cells in real time [75].…”

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…The authors suggested that this technique could be used to evaluate cell-based therapies, by providing timely feedback about cell distribution and when cell death occurs after transplantation. 64 One of the challenges in this field is to incorporate the SPIONs into the cells, as most stem cells are nonphagocytic. The incorporation of SPIONs by nonphagocytic cells can be facilitated by cationic compounds such as poly-l-lysine and protamine, due to their interaction with the negatively charged cell surface and subsequent endosomal uptake.…”

Whole body MRI of the non-human primate using a clinical 3T scanner: initial experiences

“…Among the several imaging techniques including CT, PET, SPECT, MRI, optical imaging, and ultrasound, MRI can provide high spatial and temporal resolution with the use of iron oxide-particles and 19 F-based probes for image-guided immune cell delivery and visualization of immune cell homing and engraftment, inflammation, cell physiology and gene expression (48). Available MRI techniques include using Gadoliniumbased T1 contrast agent, superparamagnetic iron oxide nanoparticles (SPIONs) based T2 contrast agent, and molecular probes containing 19 with SPIONs has been used in cell-based therapy (49,50). It has been explored previously to image immune cell (such as CD4 T+ cells, CD8 T+ cells, and Mac1+ cells) location and homing in the central nervous system of mice with superparamagnetic antibodies (51).…”