Angiogenic factors stimulate growth of adult neural stem cells.
BACKGROUND
The ability to grow a uniform cell type from the adult central nervous system (CNS) is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC) found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools.


RESULTS
Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4) and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2). These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes.


CONCLUSIONS
We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.
Androutsellis-Theotokis
Andreas
A
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. AndreasTheotokis@gmail.com
Rueger
Maria A
MA
Park
Deric M
DM
Boyd
Justin D
JD
Padmanabhan
Raji
R
Campanati
Loraine
L
Stewart
Craig V
CV
LeFranc
Yann
Y
Plenz
Dietmar
D
Walbridge
Stuart
S
Lonser
Russell R
RR
McKay
Ronald D G
RD
D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D042702:Angiopoietin-2 / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology*; D051381:Rats; D012097:Repressor Proteins; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D004268:DNA-Binding Proteins; C495457:HES3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C064045:delta protein; D005346:Fibroblast Growth Factors