Neural stem cells as novel therapeutic vehicles for genetic therapy in gliomas

Abstract

Introduction: Recent studies have demonstrated the existence of a small fraction of glioma cells (specially in high-grade tumors) endowed with features of primitive neural progenitor cells and tumor-initiating function. As such neural stem cells have tremendous migratory potential for pathological areas in the central nervous system, they, theoretically, could be used to produce a desired gene product against glioma tumor cells. Matherial and Methods: The authors perform a critical literature review in order to highlight recent studies about the role of neural stem cells in the origin of malignant gliomas as well as its possible role as novel vehicles for delivery of targeted genetic therapy approaches. Results: Several recent studies have adressed the possible role of stem cells in the origin of gliomas. Furthermore, recent evidence has also suggested that engraftment of such cells would be followed by integration into the “local neural milieu” and accompanied by stable gene expression, acting, this way, as ideal genetic “vectors”. In addition, the pluripotency of such stem cells would endow them with the capability to replace diseased tissues in an appropriate manner (such as demonstrated in animal models of ischemic stroke). Conclusions: A better understanding of the mechanisms by which neural stem cells migrate to specific sources of injury may allow us to harness these cells as vehicles for delivery of molecular therapies and impact survival in patients with high-grade gliomas. It is important to emphasize, however, that the promising use of neural stem cells for genetic therapy in gliomas, is adjunctive and not a replacement of current standart therapies such as surgery (with maximal possible resection, radiotherapy and chemotherapy (with Temozolamide), which are expected to continue being part of the therapeutic armamentary against gliomas, at least in the near future.