Year 2

Stem cell therapy has enormous potential to heal damaged organs, including the diabetic pancreas, the damaged myocardium after a heart attack, and the brain of Parkinson’s patients. However, stem cell scientists currently lack an adequate in vivo imaging method to ensure that stem cells arrive at and remain in these target organs. This would be essential for clinical adoption of stem cell therapies. Robust stem cell imaging would enable optimizing in vivo protocols to deliver, sustain, or promote differentiation of stem cells at the affected organ since each step can be validated without sacrificing the animal or using invasive tests. We need this to work well in humans, too, because a robust stem cell imaging method would enable proof of stem cell destination and fate, both of which are crucial for eventual regulatory approval as well as for clinical effectiveness.

Comparing existing imaging modalities for tracking stem cells in vivo, x-ray, CT, ultrasound, and Magnetic Resonance Imaging techniques do not provide adequate contrast, sensitivity, and spatial resolution at depth. All optical imaging methods suffer from attenuation.

A brand new imaging method, called Magnetic Particle Imaging (MPI), was invented just 6 years ago. My lab at UC Berkeley is one of the pioneers of this technology. MPI physics is fundamentally a better match to stem cell tracking than these traditional imaging methods, and it has the requisite contrast, sensitivity and safety for both human and small animal applications. Critically, we expect no attenuation with the magnetic reporting of stem cells deep within tissue. The fundamental physics offers far greater sensitivity than other imaging methods. Hence, stem cell scientists will greatly benefit from the technical development of stem cell imaging with MPI.

My research group at UC Berkeley has designed and built all four of the MPI mouse scanners that now exist in the USA. This year we have made several breakthroughs in MPI technology, including demonstrating the world’s first x-space MPI scans and the world’s first projection MPI scan. Specific to stem cell tracking applications, we have experimentally confirmed all of our key MPI physical hypotheses: the MPI signal is positive, linear and quantitative with stem cell count; the MPI signal is not attenuated when the cells are deep within tissue; and we also confirmed that MPI is very sensitive to labeled stem cells. And we are rapidly improving the one remaining significant weakness of MPI, spatial resolution, in collaboration with UW Prof. Kannan Krishnan.

Beyond these research accomplishments and publications, the CIRM Phase I grant has made possible the training of some of the finest graduate students in the world. My engineering students are excited about startup possibilities to translate our research results into genuine products so that all stem cell scientists can benefit from this cutting-edge UC Berkeley research effort.

We greatly appreciate the grant support of the CIRM Phase I Tools & Technology program, which allowed us to build, debug and radically improve MPI imaging instrumentation that will soon become an essential tool for all stem cell scientists. CIRM I support was critical for us to secure Phase II CIRM Tools and Technology support, UC Discovery grant support and NIH R01 MPI grant support.