Migration of human neural stem cells toward an intracranial glioma

Abstract

Many in vivo and in vitro studies have demonstrated the targeted migration of neural stem cells (NSC) to infiltrating brain tumors, including malignant glioma, highlighting a potential therapeutic approach. However, there is not enough information to apply this approach to clinical therapy. The most important things in stem cell therapy for brain tumors involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. By histological analysis using two different live-dyes, human NSCs were shown to migrate away from the transplanted site in the direction of the expanding C6 glioma and to intermix with the tumor bed, especially with the tumor core. This intermixing occurred within 7 days when NSCs were implanted into glioma model. The time course of migratory HB1.F5 with the greatest mobility of three NSC lines was as follows. As early as 3 days after transplantation, several NSCs were found leaving the implant site, primarily approaching microsatellites and frontier cells located near the site of NSC implantation. Through 7 days post-transplantation, massive numbers of NSCs continued to be attracted to and interspersed with C6 glioma, and were finally distributed extensively throughout the whole tumor bed, including the core and penumbra of the tumor mass. However, NSCs appeared to penetrate into the tumor mass very well, whereas normal fibroblast cells could not migrate. These findings strengthen the potential for human NSCs as attractive vehicles to improve therapeutic gene delivery to cancer or glioma if they are optimized to selectively kill neoplastic cells.

The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells

“…The migratory activity of NSCs toward the site of intracranial tumor has also been shown by several studies. [13][14][15] However, NSCs have a big obstacle for clinical application, because NSCs can only be isolated from fetal or adult brain or from embryonic stem cells, resulting in the limited use of autologous NSCs because of significant ethical issues. BMSCs are attractive as a cell vehicle, because they can be harvested without difficulty, processed efficiently in vitro, and then reinoculated into the same patient.…”

“…[14][15][16][17][18] Owing to the loss of gap junction among C6 glioma cells, it is speculated that the second mechanism may have a major role in which, to a great extent, death of the neighboring C6 cells is induced by their uptake of cytotoxic GCV triphosphate released from BMSC-TK cells after GCV treatment. As transfection of Cx43 gene into C6 cells can restore gap junction, 27,28 cytotoxic phosphorylated GCV can be transported between C6 cells through gap junction, in addition to the uptake of phosphorylated GCV through apoptotic vesicles.…”

Neural Stem Cell Tropism to Glioma: Critical Role of Tumor Hypoxia

“…The primary cells were obtained in accordance with the Guidelines of the Anatomical Pathology Department of Vancouver General Hospital, with permission to use fetal tissue granted by the Clinical Research Screening Committee Involving Human Subjects of the University of British Columbia. The HB1.F3 NSC line is a well-characterized, clonal cell line, which is nontumorigenic and multipotent in that cells from this line can be induced to differentiate into neurons, oligodendrocytes, and astrocytes (24,45,46). HB1.F3 NSCs were grown in DMEM with 10% fetal bovine serum (FBS) at 37jC in a humidified atmosphere of 6% CO 2 .…”

Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction

“…At present, no ideal treatment exits for GBM and the median survival rate of patients with GBM remains less than 1 year after diagnosis. Despite recent advances in surgical resection, radiation therapy, and chemotherapy, the prognosis of glioblastoma continues to be dismal (3)(4)(5). Exploring novel therapeutic agents and their molecular mechanism are, therefore, necessary for improving the outcome of glioblastoma treatment.…”