DESIGN AND ENGINEERING OF NEURAL STEM CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS FOR REGENERATION AND REPAIR OF MULTIPLE SCLEROSIS
The goal of this proposal is to design and engineer neural stem cells that have been derived from several lines of human embryonic stem cells. We will use both lines established on mouse cell feeders (NIH approved) and on human feeders (non-NIH approved). The cells will be specifically designed to serve as prototypes for the treatment of multiple sclerosis (MS). MS is a disease of young adults that is chronic and due to the destruction of white matter and the nerves that course through it. The destruction is due to the inflammatory response characterized by cells and substances. Some of these substances called cytokines and chemokines are destructive and some are helpful in repairing the disease. We plan to engineer cells to either secrete the positive substances or to inhibit the negative influences that have been shown to affect stem cells. We will transplant these cells into different models of MS that have similar clinical course, immunology and pathology as the human disease.
We believe that very soon human stem cell lines that have been grown under GMP conditions without contamination from other species and meet FDA specifications for human use will become available. One of the diseases that we think will be an early target of stem cell treatment will be multiple sclerosis (MS). All treatments of MS use a preclinical model of murine experimental allergic encephalomyelitis prior to Phase 1 human trials. The studies proposed here will have addressed the preclinical issues such as which cell to use (more or less differentiated), survival within a hostile inflammatory environment, efficacy in repair and regeneration, allelic variability in the host, whether murine or human feeders are factors in the ability of donor cells to repair MS damage and the questions related to tumor formation, transdifferentiation and rejection. Laboratories both in California industries and universities will require this information before considering Phase 1-2 studies in humans. This data will place them in an advanced position for manufacturing the cells for a specific disease.