Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons

Király, Marianna; Porcsalmy, Balázs; Pataki, Ágnes; Kádár, Kristóf; Jelitai, Márta; Molnár, Bálint; Hermann, Péter; Gera, István; Grimm, Wolf-Dieter; Ganß, Bernhard; Zsembery, Ákos; Varga, Gábor

doi:10.1016/j.neuint.2009.03.017

Cited by 172 publications

(224 citation statements)

References 48 publications

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“…When investigating the neural differentiation potential of MSC, the success of differentiation is often based on the expression of certain neural markers like nestin, ␤ -III-tubulin, neurofilament [Safford et al, 2002;Tropel et al, 2006;Alexanian et al, 2008;Arthur et al, 2008;Kiraly et al, 2009;Karaoz et al, 2010]. Although some neural markers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Expression Pattern of Basal Markers in Human Dental Pulp Stem Cells and Tissue

Martens

Wolfs

Struys

et al. 2012

Cells Tissues Organs

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Dental pulp stem cells (DPSC) have been characterized as a multipotent stem cell population, with the ability to differentiate into mesodermal and neural cell lineages. Although ‘de novo’ expression of neural markers after differentiation is mostly considered as proof of differentiation, expression of these markers in undifferentiated DPSC is not well described. Therefore, an immunocytochemical analysis was performed to evaluate the neural marker expression of undifferentiated human DPSC (hDPSC) in in vitro cultures. Undifferentiated hDPSC uniformly expressed neural markers β-III-tubulin, S100 protein and synaptophysin. A subset of the population showed a positive immune-reactivity for galactocerebroside, neurofilament and nerve growth factor receptor p75. Furthermore, the location of possible stem cell niches, present in young dental pulp tissue, was determined by means of immunohistochemistry based on mesenchymal and neural marker expression. The results demonstrated the presence of a perivascular niche and a second stem cell niche at the cervical area. In adult dental pulp, only a perivascular niche could be observed. Based on the expression of neural markers in naïve DPSC, it has to be taken into account that not only the marker expression upon neural differentiation must be analyzed, but an ultrastructural analysis of the morphological changes and functional studies must also be performed to confirm a successful differentiation.

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Section: Discussionmentioning

confidence: 99%

Expression Pattern of Basal Markers in Human Dental Pulp Stem Cells and Tissue

Martens

Wolfs

Struys

et al. 2012

Cells Tissues Organs

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“…They are thought to originate from the cranial neural crest and express early mesenchymal and neuroectodermal stem cell markers (11). In addition, they can differentiate into functional neurons and oligodendrocytes under the appropriate conditions (12)(13)(14). SHEDs exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases.…”

Section: Ultiple Sclerosis (Ms) and Its Animal Model Experimental mentioning

confidence: 99%

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Shimojima

Takeuchi

Jin

et al. 2016

The Journal of Immunology

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Multiple sclerosis (MS) is a major neuroinflammatory demyelinating disease of the CNS. Current MS treatments, including immunomodulators and immunosuppressants, do not result in complete remission. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells derived from dental pulp. Both SHED and SHED-conditioned medium (SHED-CM) exhibit immunomodulatory and regenerative activities and have the potential to treat various diseases. In this study, we investigated the efficacy of SHED-CM in treating experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. EAE mice treated with a single injection of SHED-CM exhibited significantly improved disease scores, reduced demyelination and axonal injury, and reduced inflammatory cell infiltration and proinflammatory cytokine expression in the spinal cord, which was associated with a shift in the microglia/macrophage phenotype from M1 to M2. SHED-CM also inhibited the proliferation of myelin oligodendrocyte glycoprotein–specific CD4+ T cells, as well as their production of proinflammatory cytokines in vitro. Treatment of EAE mice with the secreted ectodomain of sialic acid–binding Ig-like lectin-9, a major component of SHED-CM, recapitulated the effects of SHED-CM treatment. Our data suggest that SHED-CM and secreted ectodomain of sialic acid–binding Ig-like lectin-9 may be novel therapeutic treatments for autoimmune diseases, such as MS.

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“…Other stem cell types with similar properties may be obtained from gingival and periodontal tissues (Abe et al, 2012;Huang et al, 2009;Ibarretxe et al, 2012;Lima et al, 2017;Liu et al, 2015;Petrovic and Stefanovic, 2009) and even from periodontal inflammatory lesions, such as human periapical cysts (Marrelli et al, 2013;Marrelli et al, 2015;. Similarly to NC-derived cells, dental stem cells are characterised by the expression of neural crest factors, such as Snail/Snai1, Slug/Snai2, Twist1, Hnk1, Pax3, Neurogenin2 and Sox10 (Kiraly et al, 2009;Schiraldi et al, 2012), and core factors including Oct4a, Sox2, Klf4, Lin28, stage specific embryonic antigen 3 antibody (Ssea1) and Nanog (Atari et al, 2012;Ferro et al, 2012;Janebodin et al, 2011;Kerkis et al, 2006;Rosa et al, 2016). Core factors are fundamental in maintaining stem cell pluripotency (Chambers and Tomlinson, 2009;Takahashi et al, 2007;Yu et al, 2007), thus suggesting that dental stem cells may present some superior features with www.ecmjournal.org V Uribe-Etxebarria et al…”

Section: Introductionmentioning

confidence: 99%

Notch/Wnt cross-signalling regulates stemness of dental pulp stem cells through expression of neural crest and core pluripotency factors

Uribe-Etxebarria¹,

Luzuriaga²,

García-Gallastegui³

et al. 2017

eCM

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Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, Rex1, Stella/ Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal. We determined that both pathways coordinate to regulate the expression of core pluripotency and NC factors in DPSCs. Pharmacological inhibition of the Notch pathway for 48 h, by the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), abolished the expression of NC and core factors. In addition, it induced a silencing of the canonical Wnt signalling and a clear reduction in the stemness potential of DPSCs, as shown by a reduced ability to generate mature, fully differentiated osteoblasts and adipocytes. Conversely, pharmacological activation of the Wnt pathway for 48 h, by either the glycogen synthase kinase 3 beta (GSK3-β) inhibitor 6-bromoindirubin-3´-oxime (BIO) or the human recombinant protein Wnt-3a, not only largely increased the expression of NC and core factors, but also increased the efficiency of DPSCs to differentiate into mature osteoblasts and adipocytes. These results showed that a short preconditioning activation of Wnt/Notch signalling by small molecules and/or recombinant proteins enhanced the stemness and potency of DPSCs in culture, which could be useful for optimising the therapeutic use of these and other tissue-specific stem cells.

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Simultaneous PKC and cAMP activation induces differentiation of human dental pulp stem cells into functionally active neurons

Cited by 172 publications

References 48 publications

Expression Pattern of Basal Markers in Human Dental Pulp Stem Cells and Tissue

Expression Pattern of Basal Markers in Human Dental Pulp Stem Cells and Tissue

Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

Notch/Wnt cross-signalling regulates stemness of dental pulp stem cells through expression of neural crest and core pluripotency factors

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