Stem/Progenitor Cells from Inflamed Human Dental Pulp Retain Tissue Regeneration Potential

Alongi, Dominick J.; Yamaza, Takayoshi; Song, Yingjie; Fouad, Ashraf F.; Romberg, Elaine; Shi, Songtao; Tuan, Rocky S.; Huang, George T.‐J.

doi:10.2217/rme.10.30

Cited by 241 publications

(237 citation statements)

References 40 publications

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“…Recent studies have reported the presence of viable stem cells in inflamed human dental pulps (Alongi et al 2010;Wang et al 2010;Pereira et al 2012). Our study also demonstrated that DPSCs isolated from teeth that were clinically diagnosed as IP preserved similar stem cell properties as DPSCs derived from healthy pulp, including morphology, colony-forming ; C, D) were seeded in the upper chamber.…”

Section: Discussionsupporting

confidence: 75%

DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis

et al. 2016

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Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophagesessential cell players of the pulpal innate immunity-can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor α (TNF-α) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-α, the secreted level of interleukin 1β was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-α secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I-DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-α/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair.

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Section: Discussionsupporting

confidence: 75%

DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis

et al. 2016

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“…13,51 In addition to the growing evidence that stem cells can be isolated from clinically inflamed human tissue, there are also indications that these 'inflamed' cells have a stronger potential to migrate. 52,53 All of these findings suggest that inflammatory conditions can enhance stem cell migration potential. In the current study, the data from our transwell assays demonstrated more obvious increases in cell migration in the inflammation and hypoxia groups compared to the controls.…”

Section: Discussionmentioning

confidence: 97%

Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli

Gao

et al. 2016

Cell Adhesion & Migration

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Directing cell trafficking toward a target site of interest is critical for advancing stem cell therapy in clinical theranostic applications. In this study, we investigated the effects of inflammatory and/or hypoxic stimuli on the migration of bone marrow mesenchymal stem cells (BMMSCs) during in vitro culture and after in vivo implantation. Using tablet scratch experiments and observations from a transwell system, we found that both inflammatory and hypoxic stimuli significantly enhanced cell migration. However, the combination of inflammatory and hypoxic stimuli did not result in a synergistic effect. The presence of stromal cell-derived factor-1 (SDF-1) significantly enhanced cell migration irrespective of the incubation conditions, and these positive effects could be blocked by treatment with AMD3100. Based on a time course experiment, we found that preconditioning cells with either inflammatory or hypoxic stimuli for 24 h or with both stimuli for 12 h led to high levels of chemokine receptor type 4 (CXCR4) expression. In vivo studies further demonstrated that pretreatment of BMMSCs with inflammatory and/or hypoxic stimuli resulted in an increased number of systemically injected cells migrating toward skin injuries, and local SDF-1 administration significantly increased cell migration. These findings suggest that in vitro control of either inflammatory or hypoxic stimuli has significant potential to enhance SDF-1-directed BMMSC migration via the upregulation of CXCR4 expression. Although combining the stimuli did not necessarily lead to a synergistic effect, the potential to reduce the dose and time required for cell preconditioning indicates that combinations of various strategies warrant further exploration.

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“…35 The dental tissues are recognized as important sources of adult MSCs. These cells may be found in different compartments of dental structures such as the dental pulp stem cells (DPSCs), 36 periodontal ligament stem cells, 37 inflamed periapical progenitor cells, 38 and stem cells of the apical papilla (SCAP). 39 The latter (SCAP) likely represent the main MSC population involved in the regenerative endodontic procedures due to their anatomical location and relative abundance in immature teeth.…”

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confidence: 99%

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

Almeida

Chen

Henry

et al. 2014

Tissue Engineering Part A

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Regenerative endodontic procedures have become a valuable alternative for the treatment of immature teeth with pulp necrosis. In addition to resolution of periradicular pathosis and promotion of continued root development, positive vitality testing has been observed in some regenerative clinical cases. Importantly, the positive response to electric stimulation of the regenerated tissue requires targeting of periradicular axons into the previously empty root canal space. However, the mechanism by which this process occurs is largely unknown. Since stem cells of the apical papilla (SCAP) have been proposed to populate the root canal following regenerative endodontic procedures, we hypothesized that SCAP regulate neurite outgrowth and axonal targeting. To test this hypothesis, we established primary co-cultures of human SCAP and rat trigeminal neurons, and performed neurite outgrowth assays using ELISA and confocal microscopy to determine the effect of increasing concentration of SCAP on the total neurite outgrowth and axonal targeting. In addition, we evaluated whether SCAP evoked axonal targeting in vivo using a matrigel subcutaneous implant assay. Data were analyzed by ANOVA with Bonferroni's post hoc test, and significance was set at p < 0.05. The results demonstrated that SCAP release a soluble factor that regulates neurite outgrowth from cultured trigeminal neurons. Next, we demonstrated that this effect is completely abolished by pretreatment with a neutralizing antibody to brain-derived neurotrophic factor (BDNF), but not by antibodies to other neurotrophins. Further, SCAP release BDNF in a concentration-dependent manner as detected by ELISA, and trigger directed axonal targeting both in vitro and in vivo as demonstrated by microfluidic and matrigel implant experiments, respectively. Collectively, these results suggest that SCAP may be responsible for the chemical signal driving axons to target regenerated tissue via a BDNF-dependent mechanism.

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Stem/Progenitor Cells from Inflamed Human Dental Pulp Retain Tissue Regeneration Potential

Abstract: Background-Potent stem/progenitor cells have been isolated from normal human dental pulps termed dental pulp stem cells (DPSCs). However, it is unknown whether these cells exist in inflamed pulps (IPs).

Cited by 241 publications

References 40 publications

DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis

DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis

Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

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