title: Methacrylate-endcapped caprolactone and FM19G11 provide a proper niche for spinal cord-derived neural cells.
abstract: Spinal cord injury (SCI) is a cause of paralysis. Although some strategies have been proposed to palliate the severity of this condition, so far no effective therapies have been found to reverse it. Recently, we have shown that acute transplantation of ependymal stem/progenitor cells (epSPCs), which are spinal cord-derived neural precursors, rescue lost neurological function after SCI in rodents. However, in a chronic scenario with axon repulsive reactive scar, cell transplantation alone is not sufficient to bridge a spinal cord lesion, therefore a combinatorial approach is necessary to fill cavities in the damaged tissue with biomaterial that supports stem cells and ensures that better neural integration and survival occur. Caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) is a monomer [obtained as a result of ε-caprolactone and 2-hydroxyethyl methacrylate (HEMA) ring opening/esterification reaction], which can be processed to obtain a porous non-toxic 3D scaffold that shows good biocompatibility with epSPC cultures. epSPCs adhere to the scaffolds and maintain the ability to expand the culture through the biomaterial. However, a significant reduction of cell viability of epSPCs after 6 days in vitro was detected. FM19G11, which has been shown to enhance self-renewal properties, rescues cell viability at 6 days. Moreover, addition of FM19G11 enhances the survival rates of mature neurons from the dorsal root ganglia when cultured with epSPCs on 3D CLMA scaffolds. Overall, CLMA porous scaffolds constitute a good niche to support neural cells for cell transplantation approaches that, in combination with FM19G11, offer a new framework for further trials in spinal cord regeneration.
authors.affiliation: Neuronal Regeneration Laboratory, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Valdes-Sánchez
authors.affiliation: Neuronal Regeneration Laboratory, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rodriguez-Jimenez
authors.affiliation: Centre for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Spain.
authors.forename: Dunia M
authors.initials: DM
authors.lastname: García-Cruz
authors.affiliation: Centre for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Spain.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Escobar-Ivirico
authors.affiliation: Neuronal Regeneration Laboratory, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alastrue-Agudo
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain.
authors.forename: Slaven
authors.initials: S
authors.lastname: Erceg
authors.affiliation: Centre for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Monleón
authors.affiliation: Neuronal Regeneration Laboratory, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno-Manzano
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007783:Lactones / Q000494:pharmacology*; D008689:Methacrylates / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D055153:Stem Cell Niche / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001549:Benzamides; D002208:Caproates; C555528:FM19G11; D007783:Lactones; D008689:Methacrylates; C121056:caprolactone
keywords: biomaterials; ependymal stem cells; pharmacology; spinal cord injury