A comparison between stem cells from the adult human brain and from brain tumors.
OBJECTIVE
To directly compare stem cells from the normal adult human brain (adult human neural stem cells [AHNSC]), Grade II astrocytomas (AC II), and glioblastoma multiforme (GBM), with respect to proliferative and tumor-forming capacity and differentiation potential.


METHODS
Cells were isolated from tissue obtained during epilepsy surgery (AHNSCs) or tumor surgery (glioma stem cells [GSC]). They were cultured and investigated in vitro or after transplantation in immunodeficient mice.


RESULTS
Under identical experimental conditions, the following were found: 1) GBM stem cells formed tumors after orthotopic transplantation; AHNSCs showed no sign of tumor formation; 2) GSCs showed a significantly higher growth rate and self-renewal capacity; 3) both the growth rate and telomerase expression were high in GSCs and correlated with malignancy grade (GBM higher than AC II); AHNSCs had low telomerase expression; 4) GSCs invaded normal neurospheres, not vice versa; 5) both AHNSCs and stem cells from AC II and GBM responded to differentiation cues with a dramatic decrease in the proliferation index (Ki-67); 6) GSCs differentiated faster than AHNSCs; 7) upon differentiation, AHNSCs produced normal glia and neurons; GSCs produced morphologically aberrant cells often expressing both glial and neuronal antigens; and 8) differentiation of AHNSCs resulted in 2 typical functional phenotypes: neurons (high electrical membrane resistance, ability to generate action potentials) and glial cells (low membrane resistance, no action potentials). In contrast, GSCs resulted in only 1 functional phenotype: cells with high electrical resistance and active membrane properties capable of generating action potentials.


CONCLUSIONS
AHNSCs and stem cells from AC II and GBM differ with respect to proliferation, tumor-forming capacity, and rate and pattern of differentiation.
Varghese
Mercy
M
Vilhelm Magnus Laboratory, Institute for Surgical Research, University of Oslo, Oslo, Norway. mercy.varghese@medisin.uio.no
Olstorn
Havard
H
Sandberg
Cecilie
C
Vik-Mo
Einar O
EO
Noordhuis
Paul
P
Nistér
Monica
M
Berg-Johnsen
Jon
J
Moe
Morten C
MC
Langmoen
Iver A
IA
D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D013234:Stem Cells / Q000145:classification / Q000473:pathology* / Q000502:physiology*