Year 4/NCE

Damaged organs such as the diabetic pancreas, the damaged myocardium after a heart attack, and the brain of Parkinson’s patients weaken a person’s quality of life and health. Stem cell therapy has the great potential to heal these damaged organs.

Unfortunately, stem cell researchers currently lack an adequate in vivo imaging method to ensure that stem cells arrive at and remain in these target organs. This process is critical 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.

In looking at all the existing imaging modalities for tracking stem cells in vivo, including X-ray, CT, ultrasound, and Magnetic Resonance Imaging, none of these modalities have adequate contrast, sensitivity, and spatial resolution at depth to provide truly quantitative stem cell tracking data. All optical imaging methods suffer from severe attenuation. A brand new imaging method, called Magnetic Particle Imaging (MPI), was invented just under a decade 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 the traditional imaging methods (X-ray, CT, Ultrasound and MRI), 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 continued to make breakthroughs in MPI technology, including experimental demonstration of the technique in small animals. 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.

Beyond these research accomplishments, the No Cost extension period of this RT2 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 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.