Artikel
Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival
Glioblastom induzierte Migration endogen neuraler Stammzellen ist verbunden mit erhöhtem Überleben
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Neural precursor cells contribute to adult neurogenesis and to limited attempts of brain repair after injury. The migratory capacity and an apparent tropism of immortalized precursor cells for glioblastoma are known and recommended these cells as carriers for brain tumor therapy. In the present study we show that also endogenous neural precursor cells in the adult brain exhibit a strong tropism for glioblastomas in vivo and in vitro with anti-tumorigenic effect.
Methods
To determine the influence of neural precursor cells on tumor growth, we injected G261 glioma cells stably expressing DsRed either alone or together with neural precursor cells previously isolated from adult brain. We then compared the survival times after inoculation in three groups of non-transgenic recipients: one group of young (P25) and older mice (P180) received G261 tumor cells alone, whereas a third group of P180 mice obtained a 3:1 mixture of cultured adult neural precursor cells and G261 cells.
Results
The accumulation of endogenous precursor cells at the tumors decreased with age of the recipient. Our results show that the cumulative survival of younger mice significantly exceeded that of older animals when only glioblastoma cells were administered. However, when neural precursor cells were co-injected with the glioblastoma cells, the older mice reached the same survival time as young animals. Co-culturing of G261 cells together with neural precursors, but not with non-tumorigenic control cells, largely (by 80%) abrogated the increase in cell numbers normally observed with these highly proliferative tumor cells within 72h. Simultaneously, the rate of apoptosis was approximately 4 times increased in co-cultures of glioblastomas together with neural precursor compared to controls over the same time interval.
Conclusions
Our results indicate that that the presence of endogenous precursor cells is anti-tumorigenic and that this cellular interaction decreases with ageing.