UC San Diego

Stem cell therapy is an emerging tool to treat a variety of conditions from cancer to musculoskeletal disorders to cardiac disease. Current FDA-approved stem cell therapies utilize cells from peripheral blood or bone marrow to treat patients who have disorders of the hematopoietic system; however clinical trials for utilizing stem cells to treat muscular skeletal disorders and cardiac disease are underway. Because stem cells self‐renew and differentiate in multiple lineage pathways, the general theory behind stem cell therapy is that damaged tissue can be repaired or regenerated and that trophic activity of stem cells can modulate other immune cells.

While stem cell therapy has the potential to treat a variety of conditions due to its regenerative and proliferative activity, more study is needed to address ideal injection time, method of injection, distribution, and retention concerns. Imaging stem cells addresses these concerns and can provide more information overall about the fate of stem cells. Contrast agents are needed to increase the contrast and specificity of imaging stem cells. Nanoparticle‐based contrast agents are important tools for imaging because they offer high contrast and stable signal. Chapter 1 of this thesis provides a background on cell therapy and various imaging modalities. Chapter 2 details the design and synthesis of gadolinium-doped synthetic melanin nanoparticles which were used to label stem cells for photoacoustics and magnetic resonance imaging (MRI). Chapter 3 explores the mechanism of ultraviolet (UV)-induced synthetic melanin nanoparticle generation. Chapter 4 describes the design, synthesis, and application of an iron oxide PLGA-based nanoparticle used for ultrasound, photoacoustics, and magnetic particle imaging (MPI). Finally, Chapter 5 describes the synthesis and application of a nanoparticle for cancer treatment that shows an increase in photoacoustic intensity as drug is released. This nanoparticle was then used to treat tumors in mice and luminescence was used to monitor treatment response. Chapter 6 concludes with a perspective on the future of imaging cell therapy with possible directions.