Biological Use of Neural Stem Cells for Brain Tumor Therapy

Neural stem cells (NSCs) have the tremendous potential to migrate to areas of pathology in the central nervous system (CNS) (1,2). When implanted into diseased or injured CNS, NSCs can travel great distances and engraft within discrete areas as well as diffuse neuronal abnormalities (1,2). Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs (1,2). In addition, the pluripotency of NSCs endows them with the capability to replace diseased CNS tissues in an appropriate manner (1,2). Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting neuroprotection and/or regeneration of host neural pathways (1–4). These characteristics of NSCs make them ideal agents for the treatment of various CNS pathologies, especially brain tumors (1,2). BIOLOGICAL USE OF NEURAL STEM CELLS FOR BRAIN TUMOR THERAPY Brain tumors are generally difficult to treat because of the unique neuroanatomical location of the lesions next to critical neurovascular structures (1,5,6). In addition, the extensive infiltrative nature of the tumor cells makes their effective and total eradication challenging. These difficulties are reflected in the high rate of treatment failure and disease recurrence (1). In addition, normal brain structures are distorted and often destroyed by the growing neoplasm (1). Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state (1,3,4). The inherent tumor tropism of NSCs to primary and invasive tumor foci can be exploited to deliver therapeutic agents to invasive brain tumor cells in humans (1,2). NSCs have tremendous potential to migrate to the pathological brain areas. When implanted into a diseased or injured nervous system, NSCs can travel great distances to, and engraft within, target areas (1). Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs (1,7). The use of such a strategy to convert prodrug to drug via therapeutic transgenes delivered by immortalized therapeutic NSC lines has shown efficacy in animal models (1,2). In addition, the pluripotency of NSCs endows them with the capability to replace diseased (neural) tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways (1,7). These characteristics of NSCs may make them ideal agents for the treatment of brain tumors (1,2).