Background & Aim Cell therapy has shown significant promise in treating disease. Unfortunately, stem cell therapy is limited by mis-injection into highly fibrotic tissues, poor cell survival due to ischemia and inflammation, and low cell retention. For these reasons, our group has developed a variety of tools that facilitae real-time imaging of stem cell therapy. We are particualrly intersted in acoustic and photoacoustic imaging because of their low cost, ease of use, and video frame rates to faciliate real-time imaging of the cell delivery event as well as downstream analysis of cell biodistribution. We have built several novel nanoparticles contrast agents and used them image mesenchymal stem cell delivery and location in vivo. These same nanoparticles can often also provide MRI signal or deliver pro-survival drugs in addition to reporting the location of the therapeutic cells. Methods, Results & Conclusion Here, I will discuss the value of acoustic imaging as applied to cell therapy using cardiac cell therapy as an example. This work used a biocompatible multi-functional silica-iron oxide nanoparticle (SIO) made via an in situ growth of Fe3O4 nanoparticles on both the external surfaces and pore walls of mesocellular foam silica nanoparticles. In contrast to prior work, this approach builds a magnetic moiety inside the pores of a porous silica structure. These materials serve three roles: drug delivery, magnetic manipulation, and imaging. The addition of Fe3O4 to the silica nanoparticles increased their colloidal stability, T2-based magnetic resonance imaging (MRI) contrast, and superparamagnetism. The particle core offered acousticv signal. We then used the hybrid materials as a sustained release vehicle of insulin-like growth factor—a pro-survival agent that can increase cell viability. In vivo rodent studies show that labeling stem cells with this nanoparticle increased the efficacy of stem cell therapy in a ligation/reperfusion model. The nanoparticle-labeled cells increase the mean left ventricular ejection fraction by 11% and 21% and the global longitudinal strain by 24% and 34% on days 30 and 60, respectively. In summary, this multifunctional nanomedicine improves stem cell survival via the sustained release of pro-survival agents.
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