Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons.
Strategies to enhance neural stem/precursor cell (NPC) capacity to yield multipotential, proliferative, and migrating pools of cells that can efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. Here, we have generated a lentiviral vector for expression of insulin-like growth factor-I (IGF-1) and investigated the impact of IGF-1 transduction on the properties of cultured NPCs (IGF-1-NPCs). Under proliferative conditions, IGF-1 transduction promoted cell cycle progression via cyclin D1 up-regulation and Akt phosphorylation. Remarkably upon differentiation-inducing conditions, IGF-1-NPCs cease to proliferate and differentiate to a greater extent into neurons with significantly longer neurites, at the expense of astrocytes. Moreover, using live imaging we provide evidence that IGF-1 transduction enhances the motility and tissue penetration of grafted NPCs in cultured cortical slices. These results illustrate the important consequence of IGF-1 transduction in regulating NPC functions and offer a potential strategy to enhance the prospective repair potential of NPCs.
Kouroupi
Georgia
G
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
Lavdas
Alexandros A
AA
Gaitanou
Maria
M
Thomaidou
Dimitra
D
Stylianopoulou
Fotini
F
Matsas
Rebecca
R
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016086:Lentivirus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D013234:Stem Cells / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods
D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; C519530:insulin-like growth factor-1, mouse; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D006918:Hydroxyurea