Longitudinal stem cell tracking within mouse brain using Magnetic Particle Imaging

Stem cell-based therapies are emerging as novel and innovative approaches to treat neurological diseases. The successful development of these therapeutics will rely upon validating the safety and efficacy of this approach in rodent models to facilitate its translation to the clinic. A significant hurdle in this process lies in the methods used to assess the successful integration and long-term viability of transplanted cells. Longitudinal non-invasive imaging of transplanted cells is in its infancy, and a majority of studies still use separate experimental cohorts sacrificed at different time points, leading to inconsistent data and difficulty in relating cell viability to therapeutic efficacy. There is, therefore, a critical requirement to develop reliable methods for non-invasive, repeated, quantitative tracking of implanted cells in vivo. Magnetic Particle Imaging (MPI) is a new imaging methodology which uses superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents. This breakthrough technology offers significantly enhanced sensitivity and temporal resolution compared to other imaging modalities and is therefore an excellent candidate approach through which to visualize transplanted stem cells. Here we wish to utilise this novel approach to track the integration of transplanted stem cell-derived neuronal progenitors within the brain, repeatedly, in the same animal over time. We will achieve our goal by utilising this novel method to assess the integration of cells containing SPIONs in the mouse model of chronic TLE. We are uniquely placed to perform this research as our imaging facility at the Alfred Hospital (ARA-MBI) was the first facility in the world to have access to magnetic particle imaging with Computed Tomography (CT) and Hyperthermia capabilities. ARA-MBI is on track to maintain their status as a global frontrunner in MPI technology. They are currently in talks with Dr Goodwill, CEO of Magnetic Insight to establish themselves as one of the first clinical MPI system test sites worldwide, which would have our team ideally placed to translate the outcomes of this Ideas Grant into clinical trials. This will place the Alfred Hospital as a world-leading research centre in stem cell therapies. The findings from our preclinical study will provide critical data that will inform the design of a first-in-human clinical trial that will utilise MPI and provide information about cellular integration and survival in patients with drug-resistant epilepsy at the Alfred.