Neural stem cells have an inherent tropism for neuropathology such as brain tumors. This tropism is at least partially mediated by chemoattractive factors such as vascular endothelial growth factor, which is secreted by glioma cells. A recent innovative experimental treatment strategy uses stem cells as vectors for the delivery of therapeutic molecules to dispersed malignant glioma cells. Commonly, neural stem cells are delivered via direct intraparenchymal injection or via the bloodstream. However, the yield of engrafted surviving cells is poor. In their current publication (Neuro Oncol DOI: 10.1093/neuonc/noq002, 2010), Hansen et al propose a 3-dimensional (3-D) collagen matrix as an efficient carrier and method of delivery for neural stem cells. They demonstrate that neural stem cells survive and proliferate when loaded on a 3-D collagen matrix. In the first experiment, they graft a neural stem cell-coated 3-D collagen matrix into the hemisphere contralateral to a growing glioma. One week after transplantation, neural stem cells migrate across the corpus callosum and are found dispersed throughout the tumor mass. In a second experiment, the authors use a mouse glioma resection model. Following microsurgical tumor resection, a collagen matrix-containing neural stem cells is left in the resection cavity. One week following transplantation, graft-derived neural stem cells are detected within the re-growing tumor mass as well as in the interface between brain and tumor.
While the authors address the extremely relevant issue of efficient cell delivery to the central nervous system, this study has some limitations. First, since the neural stem cells used in this study were derived from mouse brain, it is unclear if human neural stem cells will also thrive when loaded onto the 3-D collagen matrix. Second, the experimental tumors are generated by the injection of a tumor cell line grown in fetal bovine serum. Since these tumors bear little resemblance to the original tumor from which they were derived, it remains to be demonstrated if a human glioma will interact with neural stem cells in a similar fashion. Despite these potential limitations, however, the authors present a novel approach to cell delivery into a surgical resection cavity. It will be interesting to see if more efficient delivery will enhance the therapeutic benefit of stem cells-based treatment strategies for malignant glioma.
CHRISTOPH P. HOFSTETTER
JOHN A. BOOCKVAR