title: Paracrine Maturation and Migration of SH-SY5Y Cells by Dental Pulp Stem Cells.
abstract: Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC secretome had a significant chemoattractive effect on SH-SY5Y cells as shown by a transwell assay. To evaluate neural maturation, SH-SY5Y cells were first induced toward neuronal cells, after which they were exposed to the hDPSC secretome. In addition, SH-SY5Y cells subjected to the hDPSC secretome showed increased neuritogenesis compared with nonexposed cells. Maturated cells were shown to increase immune reactivity for neuronal markers compared with controls. Ultrastructurally, retinoic acid (RA) signaling and subsequent exposure to the hDPSC secretome induced a gradual rise in metabolic activity and neuronal features such as multivesicular bodies and cytoskeletal elements associated with cellular communication. In addition, electrophysiological recordings of differentiating cells demonstrated a transition toward a neuronal electrophysiological profile based on the maximum tetrodotoxin (TTX)-sensitive, Na+current. Moreover, conditioned medium (CM)-hDPSC-maturated SH-SY5Y cells developed distinct features including, Cd2+-sensitive currents, which suggests that CM-hDPSC-maturated SH-SY5Y acquired voltage-gated Ca2+channels. The results reported in this study demonstrate the potential of hDPSCs to support differentiation and recruitment of cells with neuronal precursor characteristics in a paracrine manner. Moreover, this in vitro experimental design showed that the widely used SH-SY5Y cell line can improve and simplify the preclinical in vitro research on the molecular mechanisms of stem cell-mediated neuronal regeneration.
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gervois
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Wolfs
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Dillen
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Hilkens
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Ratajczak
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: R B
authors.initials: RB
authors.lastname: Driesen
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Vangansewinkel
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Bronckaers
authors.affiliation: 2 Group of Physiology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Brône
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Struys
authors.affiliation: 1 Morphology Research Group, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Lambrichts
mesh_terms: D000293:Adolescent; D002450:Cell Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D017077:Culture Media, Conditioned; D003782:Dental Pulp / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D009447:Neuroblastoma / Q000473:pathology*; D055495:Neurogenesis / Q000502:physiology*; D019899:Paracrine Communication; D014212:Tretinoin / Q000494:pharmacology; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D014212:Tretinoin
keywords: SH-SY5Y neuroblastoma cells; human dental pulp stem cells; in vitro model; migration assays; neuritogenesis; paracrine-mediated maturation