Effects of Stem Cell Factor on Cell Homing During Functional Pulp Regeneration in Human Immature Teeth

Abstract

Conventional root canal treatment in immature permanent teeth can lead to early tooth loss in children because root formation is discontinued. We investigated whether the stem cell factor (SCF) could facilitate cell homing in the pulpless immature root canal and promote regeneration of a functional pulp. In vitro, human mesenchymal stem cells (hMSCs) were exposed to SCF at various concentrations for assessing cell migration, proliferation, and differentiation toward odonto/osteoblasts by 3D-chemotaxis slides, WST-1 assay, and alkaline phosphatase activity, respectively. Fibrin gels were used to deliver 15 g/mL SCF for in vivo experiments. The release kinetic of SCF was assessed in vitro. Two corresponding human immature premolars, with or without SCF, were placed at rat calvariae for 6 and 12 weeks. All tooth specimens were either analyzed histologically and the percentage of tissue ingrowth determined or the cells were extracted from the pulp space, and the mRNA level of DMP1, DSPP, Col1, NGF, and VEGF were assessed by quantitative polymerase chain reaction. In the presence of SCF, we saw an increase in hMSCs directional migration, proliferation, and odonto/osteogenic differentiation. SCF also increased the extent of tissue ingrowth at 6 weeks but not at 12 weeks. However, at this time point, the formed tissue appeared more mature in samples with SCF. In terms of gene transcription, DMP1, Col1, and VEGF were the significantly upregulated genes, while DSPP and NGF were not affected. Our results suggest that SCF can accelerate cell homing and the maturation of the pulp-dentin complex in human immature teeth. Conventional root canal treatment in immature permanent teeth can lead to early tooth loss in children because root formation is discontinued. We investigated whether the stem cell factor (SCF) could facilitate cell homing in the pulpless immature root canal and promote regeneration of a functional pulp. In vitro, human mesenchymal stem cells (hMSCs) were exposed to SCF at various concentrations for assessing cell migration, proliferation, and differentiation toward odonto/osteoblasts by 3D-chemotaxis slides, WST-1 assay, and alkaline phosphatase activity, respectively. Fibrin gels were used to deliver 15 mg/mL SCF for in vivo experiments. The release kinetic of SCF was assessed in vitro. Two corresponding human immature premolars, with or without SCF, were placed at rat calvariae for 6 and 12 weeks. All tooth specimens were either analyzed histologically and the percentage of tissue ingrowth determined or the cells were extracted from the pulp space, and the mRNA level of DMP1, DSPP, Col1, NGF, and VEGF were assessed by quantitative polymerase chain reaction. In the presence of SCF, we saw an increase in hMSCs directional migration, proliferation, and odonto/ osteogenic differentiation. SCF also increased the extent of tissue ingrowth at 6 weeks but not at 12 weeks. However, at this time point, the formed tissue appeared more mature in samples with SCF. In terms of gene transcription, DMP1, Col1, a...

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

“…A variety of exogenous growth factors have been determined in vitro on their potentials in enhancing PSC migration, proliferation, and differentiation. Regarding induced migration, SDF‐1, basic fibroblast growth factor (bFGF), stem cell factor (SCF), and granulocyte‐colony stimulating factor (GCSF) exhibit superior potentials. Considering the proliferation, SCF, bFGF and GCSF, as well as Wnt3a are capable of promoting cell proliferation.…”

“…Regarding induced migration, SDF‐1, basic fibroblast growth factor (bFGF), stem cell factor (SCF), and granulocyte‐colony stimulating factor (GCSF) exhibit superior potentials. Considering the proliferation, SCF, bFGF and GCSF, as well as Wnt3a are capable of promoting cell proliferation. Given the differentiation, BMP‐7, BMP‐2, and GCSF represent significant advantages on dentinogenesis.…”

“…Afterward, simplified approaches are conducted extensively to minimize delivery cumbersomeness and cost of regenerative endodontics. Diverse single delivery strategies, including bFGF, GCSF, SDF‐1, and SCF, have been demonstrated ectopically in tooth segments.…”

Iodixanol as a Contrast Agent in a Fibrin Hydrogel for Endodontic Applications

“…It can be applied into the root canal system using for example a lentulo spiral. In contrast, the mere fibrin hydrogel diluted with TBS, which is commonly used as a control (Ruangsawasdi et al, 2014, 2017), is not easy to administer into the root canal system because of its immediate gelation.…”

“…The two components of the sealant were diluted to obtain a control fibrin hydrogel as previously described (Ruangsawasdi et al, 2017). To prepare the control hydrogels, the thrombin component and the fibrinogen component were diluted in Tris-buffered saline (TBS) and then mixed as described below.…”