title: Neural stem/progenitor cells differentiate into oligodendrocytes, reduce inflammation, and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury.
abstract: The central nervous system has limited capacity for regeneration after traumatic injury. Transplantation of neural stem/progenitor cells (NPCs) has been proposed as a potential therapeutic approach while insulin-like growth factor I (IGF-I) has neuroprotective properties following various experimental insults to the nervous system. We have previously shown that NPCs transduced with a lentiviral vector for IGF-I overexpression have an enhanced ability to give rise to neurons in vitro but also in vivo, upon transplantation in a mouse model of temporal lobe epilepsy. Here we studied the regenerative potential of NPCs, IGF-I-transduced or not, in a mouse model of hippocampal mechanical injury. NPC transplantation, with or without IGF-I transduction, rescued the injury-induced spatial learning deficits as revealed in the Morris Water Maze. Moreover, it had beneficial effects on the host tissue by reducing astroglial activation and microglial/macrophage accumulation while enhancing generation of endogenous oligodendrocyte precursor cells. One or two months after transplantation the grafted NPCs had migrated towards the lesion site and in the neighboring myelin-rich regions. Transplanted cells differentiated toward the oligodendroglial, but not the neuronal or astrocytic lineages, expressing the early and late oligodendrocyte markers NG2, Olig2, and CNPase. The newly generated oligodendrocytes reached maturity and formed myelin internodes. Our current and previous observations illustrate the high plasticity of transplanted NPCs which can acquire injury-dependent phenotypes within the host CNS, supporting the fact that reciprocal interactions between transplanted cells and the host tissue are an important factor to be considered when designing prospective cell-based therapies for CNS degenerative conditions.
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, 11521, Greece.
authors.forename: Paraskevi N
authors.initials: PN
authors.lastname: Koutsoudaki
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, 11521, Greece.
authors.forename: Florentia
authors.initials: F
authors.lastname: Papastefanaki
authors.affiliation: Biology-Biochemistry Laboratory, Department of Basic Sciences, Faculty of Nursing, University of Athens, Athens, 11527, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Stamatakis
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, 11521, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kouroupi
authors.affiliation: Light Microscopy Unit, Hellenic Pasteur Institute, Athens, 11521, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Xingi
authors.affiliation: Biology-Biochemistry Laboratory, Department of Basic Sciences, Faculty of Nursing, University of Athens, Athens, 11527, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Stylianopoulou
authors.affiliation: Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, 11521, Greece.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Matsas
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000209:etiology* / Q000601:surgery; D019394:Ki-67 Antigen / Q000378:metabolism; D007859:Learning Disabilities / Q000209:etiology* / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D015703:Antigens, CD; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: Morris Water Maze; astrogliosis; hippocampus; insulin-like growth factor-I (IGF-I); mechanical brain trauma