Oral Plaque from Type 2 Diabetic Patients Reduces the Clonogenic Capacity of Dental Pulp-Derived Mesenchymal Stem Cells

Abstract

Type 2 diabetes (T2D) is a major metabolic disease and a key epigenetic risk factor for the development of additional clinical complications. Among them, periodontitis (PD), a severe inflammatory disease ascribable to a dysregulated physiology and composition of the oral microbiota, represents one of the most relevant complications. Periodontitis can impact the structure of the tooth and likely the stem and progenitor cell pool, which actively contributes to the periodontal microenvironment and homeostasis. Modifications of the oral plaque play a key role in the etiopathogenesis of PD caused by T2D. However, to what extent the biology of the progenitor pool is affected has still to be elucidated. In this short report, we aimed to explore the biological effects of oral plaque derived from T2D patients with PD in comparison to non-diabetic patients with PD. Oral plaque samples were isolated from T2D and non-diabetic subjects with PD. Dental pulp stem cells (DPSCs), derived from the premolar tooth, were conditioned for 21 days with oral plaque samples and tested for their clonogenic ability. Cultures were also induced to differentiate towards the osteogenic lineage, and ALP and osteocalcin gene expression levels were evaluated by real-time qPCR. Results have shown that the number of clones generated by DPSCs exposed to T2D oral plaque was significantly lower compared to controls (ctl). The multivariate analysis confirmed that the decreased clonogenesis was significantly correlated only with T2D diagnosis. Moreover, the effect of T2D oral plaque was specific to DPSCs. Indicators of osteogenic differentiation were not significantly affected. This study provides a new biological insight into the effects ascribable to T2D in PD.

Parathyroid hormone enhances the osteo/odontogenic differentiation of dental pulp stem cells via ERK and P38 MAPK pathways

“…Moreover, DPSCs exert anti-inflammatory effect and noxious soluble media secretion. They are considered as effective candidates for the production of insulin-producing cells (Bordin et al, 2019).…”

“Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126”

“…We isolated and labelled the EVs with the green fluorescent dye CFSE. Afterwards, human umbilical vein endothelial cells (HUVECs) were stimulated for 24 hours with the EV preparation (10% v/v, corresponding to the same PL volume in percentage routinely employed in cell culture [47][48][49]51 ). HUVECs were able to uptake EVs, as demonstrated by the presence of green fluorescent dots visible in the cytoplasm (Fig.…”

“…Extracellular vesicles were isolated from PL-based preparations 2,[46][47][48][49]51 by sequentially ultracentrifugation (500 rcf for 10 minutes; 2000 rcf for 10 minutes; 100,000 rcf for 1 hour). EV pellet was then resuspended to reconstitute the initial PL volume and subsequently used at 5, 10% or 20% in medium for the experiments.…”

Taking Microbiota into Consideration in Mesenchymal Stem Cell Research

“…Antibiotic-altered oral microbiota also caused decreased proliferation rate and weakened migration ability of MSCs derived from gingival mucosa (GMSCs) in mice, affecting the wound-healing process (Su et al 2018). Clinical research showed that disordered oral plaque from type 2 diabetes patients suppressed the clonogenic capacity of DPSCs in vitro (Bordin et al 2019), but clinical data are still lacking.…”