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?SMA-Expressing Perivascular Cells Represent Dental Pulp Progenitors In Vivo.

ABSTRACT: The goal of this study was to examine the contribution of perivascular cells to odontoblasts during the development, growth, and repair of dentin using mouse molars as a model. We used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions of the descendants of cells expressing the ?SMA-CreERT2 transgene to the odontoblast lineage. In vivo lineage-tracing experiments in molars showed the contribution of ?SMA-tdTomato⁺ cells to a small number of newly formed odontoblasts during primary dentinogenesis. Using an experimental pulp exposure model in molars to induce reparative dentinogenesis, we demonstrate the contribution of ?SMA-tdTomato⁺ cells to cells secreting reparative dentin. Our results demonstrate that ?SMA-tdTomato⁺ cells differentiated into Col2.3-GFP⁺ cells composed of both Dspp⁺ odontoblasts and Bsp⁺ osteoblasts. Our findings identify a population of mesenchymal progenitor cells capable of giving rise to a second generation of odontoblasts during reparative dentinogenesis. This population also makes a small contribution to odontoblasts during primary dentinogenesis.

SUBMITTER: Vidovic I

PROVIDER: S-EPMC5298392 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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αSMA-Expressing Perivascular Cells Represent Dental Pulp Progenitors In Vivo.

Vidovic I I Banerjee A A Fatahi R R Matthews B G BG Dyment N A NA Kalajzic I I Mina M M

Journal of dental research 20161113 3

The goal of this study was to examine the contribution of perivascular cells to odontoblasts during the development, growth, and repair of dentin using mouse molars as a model. We used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions of the descendants of cells expressing the αSMA-CreERT2 transgene to the odontoblast lineage. In vivo lineage-tracing experiments in molars showed the contribution of αSMA-tdTomato<sup>+</sup> cells to a small number of newly formed ...[more]

PMID: 27834664

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Project description:BackgroundDental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry.MethodsColony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests.ResultshpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation.ConclusionsThese results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

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?SMA-Expressing Perivascular Cells Represent Dental Pulp Progenitors In Vivo.

Publications

αSMA-Expressing Perivascular Cells Represent Dental Pulp Progenitors In Vivo.

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