In Vivo Imaging for the Detection and Quantitation of Transplanted Stem/Progenitor Cells in Nonhuman Primates

Stem cells hold great potential for treating a variety of human diseases, but more information is needed on how they will function once administered to patients for regenerative medicine purposes. If imaging techniques can be developed that allow the monitoring of these transplanted stem and progenitor cells over time once injected into the body, this would provide a very powerful tool to determine the fate of the cells. This proposal specifically addresses new ways to optimize the use of positron emission tomography (PET), an imaging technology currently used in the human clinical setting, for this purpose. PET is an imaging technique that produces a three-dimensional image by detection of a tracer or label that has been introduced into the body. In these studies we plan to optimize these imaging techniques when a special tag or label is attached to individual stem and progenitor cells, and address the sensitivity of the scanner for their detection. An important goal is to improve the ability to detect the small quantities of cells that may be used, and ensure that the images obtained can accurately identify the number of cells at any given location. Several factors limit the ability to detect the cells reliably in current PET scanners. These limitations include an inherent background signal which alters the ability to accurately identify the cells injected. In addition, processing of the information obtained by the PET imaging system has not been optimized for monitoring transplanted cells where the cell quantity may be very small and the tag or label used to find the cells may be difficult to detect. Further, the methods used to place the tag or label on the cells needs to balance the requirements for obtaining good imaging information without damaging the cells or altering their capabilities in the labeling process. Our plan is to investigate these crucial issues and current roadblocks in the context of stem cell imaging with the goal of substantially advancing the imaging field for stem cell therapies. We will use model systems to ensure that the techniques and applications developed and proposed for human use are safe and do not cause harm to patients of all age groups. These studies will focus on optimizing PET imaging techniques for cell quantification and identification, and develop and refine new ways to monitor cells, including those differentiated from human embryonic stem cells, for short and extended periods of time.