Activation of Neurogenesis in Multipotent Stem Cells CulturedIn Vitroand in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3
| العنوان: | Activation of Neurogenesis in Multipotent Stem Cells CulturedIn Vitroand in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3 |
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| المؤلفون: | F. RODRIGUEZ-JIMENEZ, A. VILCHES, M. PEREZ-ARAGO, E. CLEMENTE, R. ROMAN, J. LEAL, A. CASTRO, S. FUSTERO, V. MORENO-MANZANO, P. JENDELOVA, M. STOJKOVIC, S. ERCEG |
| المصدر: | Neurotherapeutics r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) |
| بيانات النشر: | SPRINGER, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | neurogenesis, stem cells, Spinal cord injury, GSK3 inhibition, axonal growth |
| الوصف: | The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/beta-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 inhibitionin vitroon 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) andin vivoon 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 beta-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. |
| تدمد: | 1933-7213 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::d0ff9aa0b0926d0c6a09989989a4b08a https://fundanet.cipf.es/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3586 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.dedup.wf.001..d0ff9aa0b0926d0c6a09989989a4b08a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19337213 |
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