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. 2019 Jul 12:11:181-193.
doi: 10.2147/CCIDE.S211893. eCollection 2019.

Proliferation, odontogenic/osteogenic differentiation, and cytokine production by human stem cells of the apical papilla induced by biomaterials: a comparative study

Eshaghali Saberi  1 , Narges Farhad-Mollashahi  1 , Fereydoon Sargolzaei Aval  2   3 , Mersad Saberi  4
Affiliations

Proliferation, odontogenic/osteogenic differentiation, and cytokine production by human stem cells of the apical papilla induced by biomaterials: a comparative study

Eshaghali Saberi et al. Clin Cosmet Investig Dent. .

Abstract

Introduction: Clinical applications of bioactive materials are increasing in biomedical tissue engineering. This study sought to assess the effect of calcium enriched mixture (CEM) cement, Biodentine, mineral trioxide aggregate (MTA), octacalcium phosphate (OCP), and Atlantik on proliferation, odontogenic/osteogenic differentiation, and pro-inflammatory cytokine production by human stem cells of the apical papilla (SCAPs).

Materials and methods: Proliferation of SCAPs treated with different biomaterials was evaluated using trypan blue exclusion test and flow cytometry. Differentiation of cells was evaluated using ALP activity, alizarin red staining, and RT-PCR. The expression of genes of pro-inflammatory cytokines was also evaluated using RT-PCR.

Results: The SCAPs treated with biomaterials showed significantly higher proliferation, increased ALP activity, higher number of calcified nodules, and up-regulation of genes related to odontogenic/osteogenic markers compared to the control group. The expression of pro-inflammatory cytokines increased in all groups compared to the control group.

Conclusion: The tested biomaterials could induce odontogenic/osteogenic differentiation in SCAPs. MTA had a greater potential for induction of differentiation of SCAPs to odontoblast-like cells while OCP had higher potential to induce differentiation of SCAPs to osteoblast-like cells (MTA↔ BD↔ CEM↔ Atlantik↔ OCP).

Keywords: apical papilla; biomaterials; odontogenic differentiation; stem cells.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Morphological characteristics of the isolated stem cells of the apical papilla (40˟): (A) Stem cells of the apical papilla (SCAPs) at day 4 of the primary culture; (B) SCAPs reached confluence at day 28.
Figure 2
Figure 2
Comparison of ALP activity of stem cells of the apical papilla (SCAPs) following exposure to different concentrations of biomaterials. The letters (a, b, c and d) represent significant differences between groups. *Indicates the highest average. Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 3
Figure 3
Comparison of the effect of biomaterials on proliferation rate of stem cells during 9 days. The superscript letters represent significant difference between groups as determined by Tukey's test. Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 4
Figure 4
Flow cytometry and proliferation index of SCAPs treated with different biomaterials (A-E) and the control group (F). Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 5
Figure 5
Alizarin red staining: calcified nodules produced by the stem cells of the apical papilla (SCAPs) following treatment with biomaterials (A) CEM cement, (B) MTA, (C) Biodentine, (D) OCP, (E) Atlantik, (F) control. Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 6
Figure 6
Comparison of calcium content of stem cells of the apical papilla (SCAPs) treated with different biomaterials. a, b, c, and d indicate Tukey’s grouping for pair-wise comparison of biomaterials. Similar letters indicate absence of a significant difference. Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 7
Figure 7
Expression of odontogenic/osteogenic genes in stem cells of the apical papilla (SCAPs) treated with different biomaterials on days 3 and 7. a, b, c and d represent significant differences between groups (a indicates  the highest  average  and d shows the lowest). Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
Figure 8
Figure 8
Expression of pro-inflammatory cytokines by stem cells of the apical papilla (SCAPs) treated with different biomaterials at 3 and 7 days.a, b, c and d represent significant differences between groups. Abbreviations: CEM, calcium enriched mixture; MTA, mineral trioxide aggregate; OCP, octacalcium phosphate.
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