Age-Dependent Impaired Neurogenic Differentiation Capacity of Dental Stem Cell is Associated with Wnt/β-Catenin Signaling

Abstract

Two kinds of dental stem cells (DSCs), dental pulp stem cells (DPSCs) and stem cells from human-exfoliated deciduous teeth (SHED), have been identified as novel populations of mesenchymal stem cells that can be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. As we know, both of them originate from the neural crest, but have distinct characteristics and functions in vitro and in vivo. The regeneration potential of DSCs declines with advanced age; however, the mechanism of the impaired potential in DSCs has not been fully explored. In this study, we investigated whether declined neurogenic differentiation capacity is associated with an altered expression of Wnt signaling-related proteins in vitro. We compared stem cells isolated from human dental pulp in two age groups: the exfoliated deciduous teeth (5-12 years), and the third permanent teeth (45-50 years). We found that the expression levels of neuron markers, such as βIII-tubulin, microtubule-associated protein 2(MAP2), tyrosine hydroxylase (TH), and Nestin were lower in the DPSCs group compared with that in the SHED group; however, in supplementation with human recombinant Wnt1 in the medium, the DPSCs were prone to neural differentiation and expressed higher levels of neurogenic markers. In summary, our study demonstrated that Wnt/β-catenin signaling may play a vital role in the age-dependent neural differentiation of DSCs. Therefore, DSCs may provide an ideal source of stem cells that can further extend their therapeutic application in nerve injury and neurodegenerative diseases.

Mucus of Achatina fulica stimulates mineralization and inflammatoryresponse in dental pulp cells

“…Earlier researchers showed that stem cells from tooth pulp can develop into bone and this bone formation activity may be useful for osseointegrated dental implants (Yamada et al, 2010). DPSCs are a type of MSCs characterized by selfrenewal and multilineage differentiation, making them an attractive choice for tissue engineering purposes, which may provide a foundation for autologous transplantation of DPSCs (Feng et al, 2013a(Feng et al, , 2013b.…”

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

“…DPSCs [51, 135–141], SHED [36, 57, 142, 143], and SCAP [4, 47, 125, 144–146] have shown enhanced potential for differentiation into a variety of neural lineages, including functionally active dopaminergic cells and glial cells, leading proposals for dental MSCs to be used for regenerative therapy of several neurodegenerative diseases [37]. Notably, dental MSCs, while still in an undifferentiated state, constitutively express markers of neural stem/progenitor, as well as mature neural cells, including SOX-2, tenascin C, ENO-2, MAP2ab, c-FOS, Nestin, Neurofilament (NEF-H and NEF-L), Glial Fibrillary Acidic Protein (GFAP), bIII-tubulin, Microtubule-Associated Protein 2 (MAP-2), and many others [143]. However, the data regarding the neural differentiation potential of dental MSCs seem to vary for different cell types and their subpopulations in the vast body of studies published to date [37], preventing safe comparative conclusions regarding the superiority of any one cell type in regenerating neural tissues.…”

“…Regarding the neuroinductive culture media, most studies use either the Neurobasal A or conventional primarily Dulbecco's Modified Eagle's Medium (DMEM)/F12 media in their neural differentiation protocols. These are used in conjunction with various neural supplements (most commonly the B27 [36, 125, 142, 144, 148, 149], but also the N2 consisting of a mixture of insulin, transferrin, progesterone, selenium, and putrescine [137] and the insulin-transferrin-selenium (ITS) supplement [54] or their combinations [143]) in a serum-free approach. Alternatively, in other studies, the media are supplemented with conventional fetal calf (FCS) or Fetal Bovine Serum (FBS) at least for the first-stage preincubation phase [135].…”

p16INK4A mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response

“…The culture medium was changed every 3 d. Cells from the third passage were used in the follow-up experiment. The specific cell markers of DP-MSCs were characterized by flow cytometric analysis, with highly positive for CD29 and CD105, but negative for CD31 and CD34 (Feng et al, 2013).…”