Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain
| Autor: | Ke Zhan, Nobutaka Horie, Gary K. Steinberg, Tonya M. Bliss, Lamiya A. Sheikh, Erin McMillan, Bruce T. Schaar, Nathan C. Manley, Guohua Sun, Robert H. Andres, Clive N. Svendsen, Hadar Keren-Gill, Marta P. Pereira, William Slikker |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Brain Infarction
Male Time Factors Cell Survival Biotin Nerve Tissue Proteins Biology Axonal Transport Brain Ischemia Corpus Callosum Rats Sprague-Dawley Rats Nude 03 medical and health sciences Fetus 0302 clinical medicine Neural Stem Cells Neuroplasticity medicine Animals Humans RNA Messenger Progenitor cell Cells Cultured 030304 developmental biology Cerebral Cortex Analysis of Variance 0303 health sciences Neuronal Plasticity Dextrans Dendrites Neural stem cell Rats Cortex (botany) Transplantation Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Cerebral cortex Vibrissae Axoplasmic transport Neurology (clinical) Stem cell Neuroscience Psychomotor Performance 030217 neurology & neurosurgery |
| Zdroj: | Andres, Robert H; Horie, Nobutaka; Slikker, William; Keren-Gill, Hadar; Zhan, Ke; Sun, Guohua; Manley, Nathan C; Pereira, Marta P; Sheikh, Lamiya A; McMillan, Erin L; Schaar, Bruce T; Svendsen, Clive N; Bliss, Tonya M; Steinberg, Gary K (2011). Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain. Brain, 134(Pt 6), pp. 1777-89. Oxford: Oxford University Press 10.1093/brain/awr094 |
| DOI: | 10.1093/brain/awr094 |
| Popis: | Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity. |
| Databáze: | OpenAIRE |
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