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Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3

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Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3

dc.contributor.author	Francisco Javier Rodriguez-Jimenez
dc.contributor.author	Vilches, Angel
dc.contributor.author	Perez-Arago, Maria Amparo
dc.contributor.author	Clemente, Eleonora
dc.contributor.author	Roman, Raquel
dc.contributor.author	Leal, Juliette
dc.contributor.author	Artero Castro, Ana
dc.contributor.author	Fustero Lardiés, Santos
dc.contributor.author	Moreno-Manzano, Victoria
dc.contributor.author	Jendelova, Pavla
dc.contributor.author	Stojkovic, Miodrag
dc.contributor.author	Erceg, Slaven
dc.date.accessioned	2022-05-10T14:30:32Z
dc.date.available	2022-05-10T14:30:32Z
dc.date.issued	2020
dc.identifier.citation	Francisco Javier Rodriguez-Jimenez Vilches, Angel Perez-Arago, Maria Amparo Clemente, Eleonora Roman, Raquel Leal, Juliette Artero Castro, Ana Fustero Lardiés, Santos Moreno-Manzano, Victoria Jendelova, Pavla Stojkovic, Miodrag Erceg, Slaven 2020 Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3 Neurotherapeutics 18 515 533
dc.identifier.uri	https://hdl.handle.net/10550/82709
dc.description.abstract	The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/β-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell-derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell-derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell-derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma-positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl-treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI.
dc.language.iso	eng
dc.relation.ispartof	Neurotherapeutics, 2020, vol. 18, p. 515-533
dc.subject	Cèl·lules mare
dc.subject	Neurones
dc.subject	Neurologia
dc.title	Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3
dc.type	journal article	es_ES
dc.date.updated	2022-05-10T14:30:32Z
dc.identifier.doi	10.1007/s13311-020-00928-0
dc.identifier.idgrec	152646
dc.rights.accessRights	open access	es_ES