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.

Heterogeneous fate choice of genetically modulated adult neural stem cells in gray and white matter of the central nervous system

“…Likewise, little is known about the influence of regional differences (GM and WM) as well as of an injury environment on transplanted aNSCs. As previous stem cell transplantation studies revealed poor fate directing properties when NSCs were, for example, instructed to differentiate into neurons prior to transplantation (Koutsoudaki et al, ) or when cells overexpressed IGF‐1 (Miltiadous et al, ), this supports a potential dominant effect of the host tissue.…”

Novel insights into SLC25A46-related pathologies in a genetic mouse model

“…For evaluation of the expression levels of vGlut1 and vGlut2, fluorescence intensity was measured as pixel intensity on single channel stacks of confocal images, acquired under the same settings, as previously described [42,43]. The laser power was set to the lowest level that would be adequate for high signal/noise ratio acquisition and would not bleach the specimen.…”

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury

“…70) Under combined treatment, osthole helps to inhibit acute inflammation at the early stages and neuronal stem cells exert the effect of reduced inflammation by themselves. 71) Apparently combined therapeutic treatment group provide a prominent better effect on the inhibition of inflammation when compared with other groups. The primary damage and secondary injury both can make cells undergo apoptosis, which represents a programmed process of cell death.…”