Engineering neural progenitor cells for the treatment of central nervous system disorders
The prognosis for patients with malignant brain tumors is grim, with a life expectancy of generally less than a year. The only successful adjuvant therapy following surgical removal of these tumors is radiation, and increasing doses increases lifespan. However, the dose is limited due to damage to normal tissue surrounding the tumor. This has lead to the exploration of alternative methods of brain tumor treatment, such as gene therapy. Unfortunately, the efficiency with which tumor cells are transfected by viral vectors is generally low, around 1% or less. Dr. Gobbel and his research team have begun to explore the theory that transplanted neural stem cells might be useful as agents to introduce gene products into the tumor environment. Such cells might also be useful at preventing or repairing normal tissue injury occurring secondary to radiation therapy of brain tumors. It has been found that neural stem cells can be isolated from the adult rat or mouse brain, grown in-vitro indefinitely, transfected with lentiviral vectors to express genes of interest and differentiated to form neurons, astroglia and oligodendroglia. In-vitro, roughly 2 out of 3 cell divisions result in the production of post-mitotic cells, and this result is consistent with a cell division model in which stem cell expansion is very limited. This may limit the ability to routinely isolate and expand these cells. However, when transplanted into brain tumors within animal models, can incorporate into the tumor milieu and continue to express the gene product. Furthermore, although radiation leads to loss of these cells, these cells can be transplanted into normal brain where they appear to have a propensity to incoporate into white matter tracks and perivascular regions. Due to these discoveries, Neural stem cells are beocming promising agents for enhancing brain tumor therapy. Further work determining their longevity and efficacy in-vivo following transplantation is currently underway.