Year 2

Stem cells offer tremendous potential to treat previously intractable diseases. However, the clinical translation of these therapies presents unique challenges. One of which is the absence of robust methods to monitor cell location and fate after delivery to the body. The delivery and biological distribution of stem cells over time can be much less predictable compared to conventional therapeutics, such as small-molecule therapeutic drugs. This basic fact can cause road blocks in the clinical translation, or in the regulatory path, which may cause delays in getting promising treatments into patients. My research aims to meet these challenges by developing new non-invasive cell tracking platforms for emerging stem cell therapies. Recent progress in magnetic resonance imaging (MRI) has demonstrated the feasibility of non-invasive monitoring of transplanted cells in patients. This project will build on these developments, by creating next-generation cell tracking technologies with improved detectability and functionality. In year 2 of this project, we have made excellent progress in developing a new generation of probes for MRI-based cell tracking. These probes are based on perfluorocarbon (PFC) emulsions and have greatly improved sensitivity over prior PFC-based probes used in clinical trials. Via novel chemical synthesis schemes, the probes incorporate metal ions in the PFC to yield agents with greatly enhanced sensitivity and data acquisition speed during the MRI scan. Using these agents, we describe preliminary assessments of the biocompatibility, cell labeling stability, and in vivo MRI cell detection studies in model systems. Overall, future improvements in sensitivity of the probes will only accelerate adoption of this technology and open up new uses for MRI cell tracking; towards this goal, the excellent stability and MRI properties of our next-generation PFC probes should advance this field.