Differences of isolated dental stem cells dependent on donor age and consequences for autologous tooth replacement

Kellner, Manuela; Steindorff, Marina M.; Strempel, J.; Winkel, Andreas; Kühnel, Mark P.; Stiesch, Meike

doi:10.1016/j.archoralbio.2014.02.014

Cited by 38 publications

(18 citation statements)

References 39 publications

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“…Furthermore, DPSCs are non-tumourigenic even after their immortalisation by telomerase overexpression (Wilson et al, 2015). Finally, given that the dental pulp is rather well preserved in mid-to-advanced age patients, DPSCs are also suitable for autologous therapy (Ibarretxe et al, 2012;Kellner et al, 2014;Wu et al, 2015).…”

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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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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“…Several reports have indicated that a reduction in proliferative ability was strongly correlated with increasing age. For example, DPSCs derived from younger individuals showed faster doubling times than those from senior individuals [39]. In addition, with increasing age, dental stem cells underwent a decline in their capacity to perform neurogenic differentiation but an increase in their capacity to perform osteogenic differentiation in vitro [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth

Diao

Wang

et al. 2014

BioMed Research International

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Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1β, IL-6, and TNF-α, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-α protein. In conclusion, our in vitro results showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration.

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“…One of its major advantages is that maxilla-derived stem cells proliferation potential is probably unaffected by donor age, and only population doubling time seems to increase with donor age. 56 BM-MSC have already been used in the alveolar cleft regeneration on animal models [17][18][19][20][21][22] and in first clinical cases. 23-28 BM-MSC were by many investigators found suitable for craniofacial tissue engineering including calvarial bone defects 57-61 and both maxillary 62 and mandibular 63-67 bone reconstruction.…”

Section: Bone Marrow-derived Stem Cellsmentioning

confidence: 99%

Stem cell regenerative therapy in alveolar cleft reconstruction

Gładysz¹,

Hozyasz²

2015

Archives of Oral Biology

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Differences of isolated dental stem cells dependent on donor age and consequences for autologous tooth replacement

Cited by 38 publications

References 39 publications

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

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

Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth

Stem cell regenerative therapy in alveolar cleft reconstruction

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