In Vivo Imaging of Human Embryonic Stem Cell Derivatives and Tumorigenicity

Human embryonic stem cells (hESCs) are one of the most fascinating subjects of interest in all of biology and medicine these days. Under certain physiologic conditions, they can be induced to become specialized cells such as brain, cardiac, liver, pancreatic, and bone marrow cells. This opens up the exciting possibility that hESCs may one day be used to treat patients with Parkinson’s disease, heart conditions, hepatitis, diabetes, and leukemia, just to name a few currently intractable diseases that affect millions of Americans alone. This field of cell-based therapies to treat human diseases is generally referred to as “regenerative medicine.”

Scientists who want to study hESCs or their specialized cell derivatives typically inject them into small animal models such as mice and rodents. However, researchers currently are unable to monitor noninvasively these cells after transplant. Instead, these animals are typically sacrificed for postmortem biopsy, which precludes long-term follow-up of transplanted cells. Without the ability to follow the progress of transplanted cells over a longer period of time, important insights into hESC fates in vivo have not been forthcoming. Thus, developing a novel technology to track transplanted hESCs and their specialized cell derivatives would represent a major advancement in this field that will produce wide-ranging theoretical and practical implications.

Another problem with transplantation of hESCs is the potential to cause teratomas. Teratomas are disorganized arrays of cell differentiation that appear to recapitulate many of the events involved in early embryonic development. Clearly, the teratoma formation risk is a major obstacle to future clinical application of hESCs. In this proposal, we will evaluate how teratoma forms in living subjects over time using the imaging techniques that we have developed as well as how best to prevent them in the first place.

Due to the serious risks posed by teratoma formation, it is necessary to induce hESCs to become specialized cell derivatives first before transplantation for therapeutic purposes. However, this process is not efficient at present despite intense efforts searching for methods to expedite it. Our team plans to tackle this problem using the latest genomics and proteomics technology.

In summary, our proposal is a targeted response to the CIRM SEED grant. It seeks to develop a novel technology (molecular imaging) that will address a critical barrier in clinical translation of hESC therapy (teratoma formation) and provide a better understanding of cardiac cell differentiation process (genomics/proteomics). Our well-established multidisciplinary team has the required training, experience, and innovation to complete the project. Overall, we are confident that our proposed studies will generate significant progress in this field, in both scientific knowledge and useful therapies.