Glioblastoma multiforme: can neural stem cells deliver the therapeutic payload and fulfill the clinical promise?

Neural stem cells (NSCs) are defined as progenitor cells of the CNS. They have the capacity for self-renewal and multipotent potential to differentiate into three major types of CNS cells: neurons, astrocytes and oligodendrocytes. Recently, NSCs have received a great deal of attention owing to their therapeutic potential for neurodegenerative and oncologic diseases. It has been speculated for many years that it may be possible to formulate a novel cell replacement platform for these diseases by harnessing NSCs’ multipotent nature. In the last decade, many in vitro and in vivo studies have demonstrated the unique migratory capacity of NSCs throughout the brain. In 2000, Aboody et al., along with several other groups, were able to show that NSCs transplanted into animal models of brain neoplasia were found near metastatic tumor beds far from their site of original transplantation [1,2]. These observations galvanized the concept of stem cell-based targeted delivery of anti cancer agents to disseminated tumors in the brain. The ability of NSCs to migrate to tumors is central to their utility as carriers of therapeutic, antineoplastic modalities. Most of the earlier preclinical studies investigating the tumor-homing properties of NSCs were performed in various animal models of intracranial glioma [1,2]. However, the ability of NSCs to seek out tumors is not limited to gliomas. Human NSCs have also been shown to target breast cancer [3] and melanoma brain metastases [4], as well as disseminated neuroblastoma [5]. The precise mechanism governing the tumor-tropic properties of NSCs is not fully understood. It is speculated that gradients of factors such as chemokines and proangiogenic growth factors produced in the distant tumor microenvironment may act as chemoattractants for NSCs. The multifaceted homing mechanisms employed by NSCs favor their use as delivery vehicles over other, largely one-dimensional, targeting strategies. Nevertheless, it remains to be seen whether NSCs can track and target glioma in the human brain. Owing to the size difference between the rodent and human brain, the distance required to track disseminated tumor cells in the human brain will be vastly larger than in the rodent brain. Ultimately, a careful characterization of these parameters in the preclinical setting will be critical for the successful translation of NSC-based cell carriers to the clinic. Most of the currently available cancer gene therapies have failed to sustain anti-tumor effects in the tumor microenvironment long enough to achieve clinically relevant therapeutic efficacy. This is partly due to the host immune Atique U Ahmed