Endogenous IGF-1 regulates the neuronal differentiation of adult stem cells

✍ Scribed by Gordon J.F. Brooker; Michael Kalloniatis; Vincenzo C. Russo; Mark Murphy; George A. Werther; Perry F. Bartlett

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 333 KB
• Volume: 59
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(20000201)59:3<332::aid-jnr6>3.0.co;2-2

✦ Synopsis

Stem cells from the adult forebrain of mice were stimulated to form clones in vitro using fibroblast growth factor-2 (FGF-2). At concentrations above 10 ng/ml of FGF-2, very few clones gave rise to neurons; however, if FGF-2 was removed after 5 days, 20 -30% of clones subsequently gave rise to neurons. The number of neuron-containing clones and the number of neurons per clone was significantly enhanced, if insulin-like growth factor (IGF)-1 or heparin were added subsequent to FGF-2 removal. The spontaneous production of neurons after FGF-2 removal was shown to be due to endogenous IGF-1, since antibodies to IGF-1 and an IGF-1 binding protein totally inhibited neuronal production. Similarly, these reagents also abrogated the neuron-promoting effects of heparin. Thus, it appears that endogenous IGF-1 may be a major regulator of stem cell differentiation into neurons. Furthermore, it was found that high levels of IGF-1 or insulin promoted the maturation and affected the neurotransmitter phenotype of the neurons generated.