Magnetic Resonance Characteristics of CNS Changes Resulting from Targeted Human Embryonic Stem Cell Administration
Regenerative medicine through the use of human embryonic stem cells (hESC) represents an emerging therapeutic approach with great promise for treating a wide range of diseases. Perhaps one of the most exciting applications is toward the regeneration of central nervous system (CNS) tissue in the hope of reversing damage due to trauma or degenerative disease. The impact of such a therapy upon the practice of neurology and upon society in general would be enormous, since, currently, such CNS trauma and degenerative disease is often irreversible or partially reversible. Such possibilities have fueled tremendous excitement and optimism among patient groups, and, now, a popular vote in California has called for intensive research to bring these therapies to the bedside as soon as is safely possible.
A pressing need, however, for the advancement of hESC therapy for CNS diseases is the ability to examine, in a rapid, efficient, and, eventually, noninvasive manner, the effects of hESCs upon the CNS. It is critical to develop such techniques 1) to track the effects of hESC administration to determine that the cells are, indeed, reaching and having an effect upon the target of interest and 2) to detect and characterize any dangerous effects that hESCs may have upon surrounding tissue, such as inflammation, scarring, or tumor formation.
Recent developments in high field magnetic resonance (MR) imaging have shown an ability to detect subtle changes in CNS tissue that, previously, could only be detected using the microscope. These "high-definition" MR imaging techniques, also known as MR microscopy, may provide the tools needed to follow the effects of hESCs over time in the living organism, thus providing the safety and efficacy information needed to proceed with human studies.
This proposal will examine central nervous system (CNS) effects of hESC administration in rats and mice with spinal cord injuries using MR microscopy. We will examine the tissue for signal changes corresponding to clinically relevant effects, including intended effects such as growth of connections between cells, but also for unintended and dangerous effects such as tissue rejection, scarring, and tumor formation. We will examine these new MR imaging techniques with the goal of providing a tool for use in human clinical trials. Therefore, in addition to imaging tissue that has been taken out of animals that have died, we will examine living animals undergoing hESC therapy for CNS injury. Our findings with MR microscopy will be directly compared to findings under the microscope to validate the technique. In addition, we will test whether or not these techniques can easily be adapted for use in clinical MR scanners already present at most hospitals.
Therefore, our research aims to define the MR techniques that will be most useful to doctors and their patients undergoing hESC therapy. Federal funding of this project is not allowed, so we are applying to CIRM.
The proposed research aims to speed the availability of human embryonic stem cell (hESC) therapies to generations of Californians who will, unfortunately, experience the deeply troubling afflictions of central nervous system (CNS) trauma and degenerative illness, including paralysis due to spinal cord injury, stroke, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and a host of other CNS afflictions not mentioned here. The researchers, if funded, will work toward providing a diagnostic tool that, first, can be used by other researchers to evaluate safety and efficacy of various hESC therapies under development, and, second, can be used by doctors to safely and effectively monitor patients undergoing clinical trials in hESC therapy. In addition to the above potential for relief of physical suffering, if successful, this research may lead to an invention that could generate significant revenue for the State of California under the revenue sharing requirements of the CIRM.