The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs)

Ahmed, Nermeen; Murakami, Masashi; Kaneko, Satoru; Nakashima, Mitsuyoshi

doi:10.1038/srep35476

Cited by 89 publications

(82 citation statements)

References 59 publications

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“…[32][33][34] Several recent studies have sought to manipulate cell spreading to control stemness during expansion. For instance, Nakashima et al 35 recently reported that MSC cultured under hypoxic conditions remained smaller in size and increased their expression of stem cell markers and had improved differentiation capacity. In addition, Wong et al 36 recently reported that MSCs cultured on hyaluronan (HA) coated TCP were smaller in size, remained largely quiescent, and maintained their differentiation potential with passage compared to MSCs cultured on untreated TCP.…”

Section: Discussionmentioning

confidence: 99%

Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness, mechano‐responsivity, and differentiation potential

Heo

Szczesny

Kim

et al. 2017

Journal Orthopaedic Research

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Mesenchymal stem cells (MSCs) hold great promise for regenerative therapies and tissue engineering applications given their multipotential differentiation capacity. However, MSC isolation and expansion are typically performed on super-physiologically stiff tissue culture plastic (TCP), which may alter their behavior and lead to unintended consequences upon implantation. In contrast, electrospun nanofibrous scaffolds possess physical and mechanical properties that are similar to that of native tissue. In this study, we investigated whether isolation and expansion of juvenile bovine MSCs directly onto electrospun nanofibrous scaffolds better preserves MSC phenotype and stemness compared to TCP. Our data show that culture of MSCs on electrospun scaffolds reduces proliferation, decreases cellular senescence, and better maintains stemness compared to cells isolated and expanded on TCP, likely due to a reduction in cell contractility. Furthermore, in contrast to electrospun scaffolds, TCP biased MSCs towards a fibrotic phenotype that persisted even after the cells were reseeded onto a different substrate. Cells pre-cultured on electrospun scaffolds exhibited a heightened response to mechanical stimuli and greater chondrogenesis in methacrylated hyaluronic acid hydrogels. These data suggest that alternative substrates that better approximate the native cell environment should be used to preserve endogenous MSC behavior and may improve their success in tissue engineering applications. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:808-815, 2018.

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Section: Discussionmentioning

confidence: 99%

Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness, mechano‐responsivity, and differentiation potential

Heo

Szczesny

Kim

et al. 2017

Journal Orthopaedic Research

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“…Hypoxic culture conditions were generated as previously described by Ahmed et al (26). H-hPDLSCs were maintained in a trigas incubator (AirTech, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Giacoppo

Rajan

Diomede³

et al. 2017

The FASEB Journal

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Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35–55. At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice. Our results demonstrate the efficacy of H-hPDLSCs-CM treatment in diminishing clinical and histologic disease score. A key finding from this study is the marked expression of anti-inflammatory cytokine IL-37, paralleled by the suppression of proinflammatory cytokines in mice with EAE that were treated with H-hPDLSCs-CM. In addition, a consequent modulation of oxidative stress, autophagic, and apoptotic markers was observed in mice with EAE after hPDLSCs-CM administration. In addition, to provide additional evidence of the molecular mechanisms that underlie H-hPDLSCs-CM, we investigated its therapeutic action in scratch injury–exposed NSC-34 neurons, an in vitro model of injury. This model reproduces severe inflammation and oxidative stress conditions as observed after EAE damage. In vitro results corroborate the ability of hPDLSCs-CM to modulate inflammatory, oxidative stress, and apoptotic pathways. Taken together, our findings suggest H-hPDLSCs-CM as a new pharmacologic opportunity for the management of MS.—Giacoppo, S., Thangavelu, S. R., Diomede, F., Bramanti, P., Conti, P., Trubiani, O., Mazzon, E. Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL-37.

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“…Classically, it was thought that HIF is involved in blood vessel application and proliferation of cancer cells (Keith & Simon 2007). However, some reports demonstrated that the HIF-1 signalling pathway is involved in wound healing and tissue regeneration (Tajima et al 2009, Ahmed et al 2016. Additionally, HIF inducers (e.g.…”

Section: Groupmentioning

confidence: 99%

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

et al. 2019

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Aim To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. Methodology The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different‐sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro‐computed tomography (micro‐CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate‐buffered saline (PBS) was also evaluated after 4 weeks using micro‐CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t‐test, one‐way ANOVA with Tukey's post hoc test, the Kruskal–Wallis test or the Steel–Dwass test. P values < 0.05 were considered statistically significant. Results TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4‐week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P < 0.05) under standardized cavity preparations. Conclusions TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.

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The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs)

Cited by 89 publications

References 59 publications

Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness, mechano‐responsivity, and differentiation potential

Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness, mechano‐responsivity, and differentiation potential

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

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