gms | German Medical Science

Objective: We have recently discovered that neural precursors from the stem cell niches of the brain are activated by glioblastomas, they are attracted to the tumor, improve animal survival in a tumor model and can directly cause tumor cell apoptosis. This appears to be an intrinsic anti-tumorigenic response, which, however, declines with increasing age. To study activation mechanisms of stem cell glioblastoma interaction we examined endogenous stem cell behavior in vitro and in vivo after application of polymeric hollow fiber, which was filled with glioblastoma cells.

Methods: A hollow fiber membrane (HFM, which was permeable for soluble substances of less than 500kDa, FiberFlo, Minntech BV, Netherlands) was filled with 7000 GL261 glioblastoma cells stably expressing DsRed in vitro and were stereotactically placed into the caudate putamen of P25 old transgenic mice expressing green fluorescent protein under the control of the nestin promoter. In a second approach dsred-GL261 filled HFM were co-cultured with neural precursor cells previously isolated from adult brain of nestin-gfp mice. Immunofluorescent triple labeling was carried out on 40-µm-free-floating sections using a spectral confocal microscope.

Results: 14 days after transplantation of GL261-dsred filled HFM into the brain of 25 day old mice nestin-gfp positive cells surrounded the glioblastoma in the same manner as previously observed with uncovered glioblastoma cells. Co-culture experiments confirmed the strong tropism of endogenous NPCs for GL261-dsred filled HFM indicate a soluble factor associate attraction of endogenous neural precursor cells by glioblastoma.

Conclusions: We developed a refillable cell encapsulation device for introducing cells into the brain while keeping them physically isolated from contact with brain tissue with a semipermeable membrane. Our results indicate that endogenous neural precursor cells were attracted towards glioblastoma by a secreted soluble factor.