The pleotrophic effects of insulin-like growth factor-I on human spinal cord neural progenitor cells.
Most stem cell therapies involve direct, intraparachymal placement of neural progenitor cells. These cells provide physical support to the endogenous neuronal population and may be engineered to provide in situ growth factor support. Insulin-like growth factor-I (IGF-I) has potent neurotrophic and neuroprotective properties and is expressed by human neural stem cells (hNSCs). IGF-I is implicated in multiple aspects of cell behavior, including proliferation, differentiation, and survival. Enhancing hNSC function through IGF-I overexpression may increase the benefits of stem cell therapy. As a first step to that goal, we examined the direct effects of IGF-I on hNSC behavior in vitro. We demonstrate that IGF-I treatment enhances both the number and length of hNSC neurites. This is correlated with a decrease in proliferation, suggesting that IGF-I promotes neurite outgrowth but not proliferation. While IGF-I activates both AKT and MAPK signaling in hNSCs, we demonstrate that IGF-I-mediated neurite outgrowth is dependent only on AKT signaling. Finally, we demonstrate that IGF-I is neuroprotective after glutamate exposure in a model of excitotoxic cell death.
Lunn
J Simon
JS
Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Pacut
Crystal
C
Backus
Carey
C
Hong
Yu
Y
Johe
Karl
K
Hefferan
Michael
M
Marsala
Martin
M
Feldman
Eva L
EL
D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology*
D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases