Roles of insulin and transferrin in neural progenitor survival and proliferation.
Multipotent neural progenitor cells or neural stem cells (NSC) can be propagated in vitro from a variety of sources and have great potential for neural repair. Although it is well known that NSC divide in response to basic fibroblast growth factor (FGF-2) and epidermal growth factor (EGF), cofactors necessary for survival and maintenance of a multipotent potential are still a matter of debate. In the current study, we examined the requirements for NSC proliferation and survival in vitro using the neurosphere culture system. Apotransferrin (TF), along with EGF and FGF-2, was sufficient for the formation of primary neurospheres derived from embryonic rat cortices. The addition of low concentrations of insulin or insulin-like growth factor-1 (IGF-1) enhanced neurosphere size and number and was necessary for continued passaging. Both insulin and IGF-1 acted at low concentrations, suggesting that their effects were mediated by their cognate receptors, both of which were expressed by neurosphere cultures. Sphere-forming progenitors survived for long periods in culture without EGF or FGF-2 when either insulin or IGF-1 was added to the media. Cell cycle analysis determined that surviving progenitors were relatively quiescent during the period without mitogens. Upon the reintroduction of EGF and FGF-2, surviving progenitors gave rise to new spheres that produced largely glial-restricted progeny compared with sister cultures. These data indicate that the neurogenic potential of NSC may be intimately linked to a continuous exposure to mitogens.
Erickson
Rebecca I
RI
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California 94025, USA.
Paucar
Andres A
AA
Jackson
Robert L
RL
Visnyei
Koppany
K
Kornblum
Harley
H
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007328:Insulin / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014168:Transferrin / Q000502:physiology*
D007328:Insulin; D014168:Transferrin