Use of neural stem cells as therapeutic vehicles for the treatment of malignant glioma

Abstract

The prognosis for patients with malignant glioma, the most common primary intracranial neoplasm, remains dismal despite significant progress in neuro-oncological therapies and technology. This stems from the inability of current treatment strategies to address the highly invasive nature of this disease. Malignant glial cells often disseminate throughout the brain, making it exceedingly difficult to target and treat all intracranial neoplastic foci with the result that tumor recurrence is inevitable despite aggressive surgery and adjuvant radio- and/or chemotherapy. The use of neural stem cells as delivery vehicles for tumor toxic molecules is a novel experimental strategy aimed specifically at targeting disseminated tumor pockets. It has been demonstrated that neural stem cells possess a robust tropism for infiltrating tumor cells and that they can be used to deliver therapeutic agents directly to tumor satellites with significant therapeutic benefit. The aim is to develop these findings into a clinically viable technology which would not be hindered by ethical and tissue rejection related concerns stemming from the use of fetal or embryonic tissue transplants. A novel technology whereby neural progenitors similar in morphology, phenotype and behavior to fetal neural stem cells can be isolated from adult bone marrow is also discussed. These technologies represent important progress in the development of a treatment strategy that can specifically target disseminated neoplastic pockets within the brain. However, despite encouraging results in preclinical models, there are significant impediments that must be overcome prior to clinical implementation of this strategy. The key among these is understanding the specific tropic mechanisms that govern neural stem cells migration towards tumors and refining the processes used to generate neural progenitors from adult bone marrow in a clinically implementable fashion. Despite these limitations, the use of neural stem cells for brain tumor therapy holds significant promise and may emerge as an important therapeutic modality for patients with malignant glioma.

• astrocytoma
• brain tumor(s)
• cellular therapy
• gene therapy
• glioma
• stem cells