BackgroundPeriodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model.MethodsIn the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation.ResultsOur study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm3) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm3) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05).ConclusionBoth hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0362-8) contains supplementary material, which is available to authorized users.

Intrinsic functional connectivity detected by functional MRI (fMRI) provides a useful but indirect approach to study the organization of human brain systems. An unresolved question is whether functional connectivity measured by resting state fMRI reflects anatomical connections. In this study we used the well-characterized anatomy of cerebrocerebellar circuits to directly test whether intrinsic functional connectivity is associated with an anatomic pathway. Eleven first episode stoke patients were scanned five times during a period of six months and eleven healthy control subjects were scanned three times within one month. In patients with right pontine stokes, the functional connectivity between the right motor cortex and the left cerebellum was selectively reduced. This connectivity pattern was reversed in patients with left pontine strokes. While factors beyond anatomical connectivity contribute to fMRI measures of functional correlation, these results provide direct evidence that functional connectivity depends upon intact connections within a specific polysynaptic pathway.

Our results have identified a new function of SFRP2 and shed new light on the molecular mechanism underlying directed differentiation of stem cells of dental origin.

IntroductionPeriodontitis is one of the most widespread infectious diseases in humans. We previously promoted significant periodontal tissue regeneration in swine models with the transplantation of autologous periodontal ligament stem cells (PDLSCs) and PDLSC sheet. We also promoted periodontal tissue regeneration in a rat model with a local injection of allogeneic bone marrow mesenchymal stem cells. The purpose of the present study is to investigate the roles of the hepatocyte growth factor (HGF) and human dental pulp stem cells (DPSCs) in periodontal tissue regeneration in swine.MethodIn the present study, we transferred an adenovirus that carried HGF gene into human DPSCs (HGF-hDPSCs) under good manufacturing practice (GMP) conditions. These cells were then transplanted into a swine model for periodontal regeneration. Twenty miniature pigs were used to generate periodontitis with bone defect of 5 mm in width, 7 mm in length, and 3 mm in depth. After 12 weeks, clinical, radiological, quantitative and histological assessment of regenerated periodontal tissues was performed to compare periodontal regeneration in swine treated with cell implantation.ResultsOur study showed that injecting HGF-hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. A hDPSC or HGF-hDPSC sheet showed superior periodontal tissue regeneration compared to the injection of dissociated cells. However, the sheets required surgical placement; thus, they were suitable for surgically-managed periodontitis treatments. The adenovirus-mediated transfer of the HGF gene markedly decreased hDPSC apoptosis in a hypoxic environment or in serum-free medium, and it increased blood vessel regeneration.ConclusionThis study indicated that HGF-hDPSCs produced under GMP conditions significantly improved periodontal bone regeneration in swine; thus, this method represents a potential clinical application for periodontal regeneration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0244-5) contains supplementary material, which is available to authorized users.

IntroductionStem cells have great therapeutic potential due to their capacity for self-renewal and their potential for differentiating into multiple cell lineages. It has been recently shown that the host immune system has fundamental effects on the fate of transplanted mesenchymal stem cells during bone repair, where the topical administration of aspirin is capable of improving calvarial bone repair in rodents by inhibiting tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production. This study investigates whether aspirin is capable of accelerating the regenerative potential of bone marrow mesenchymal stem cells (BMSC) in a mini swine calvarial bone defect model.MethodsCalvarial bone defects (3 cm × 1.8 cm oval defect) in mini swine were treated with BMSC pretreated with 75 μg/ml aspirin for 24 h seeded onto hydroxyaptite/tricalcium phosphatel (HA/TCP), or with BMSC with HA/TCP, or with HA/TCP only, or remained untreated. Animals were scanned with micro-computed tomography (microCT) at 2 days and 6 months postsurgery and were sacrificed at 6 months postsurgery with decalcified tissues being processed for histomorphometric examination. The cytokine levels, including TNF-α and IFN-γ, were measured by enzyme-linked immunosorbent assay (ELISA).ResultsAspirin at 75 μg/ml promoted the osteogenesis of BMSC in vitro and in vivo, shown by Alizarin Red staining and new bone volume in the nude mice transplantation model (p < 0.01), respectively. Defects treated with aspirin-BMSC showed significantly greater new bone fill compared with other three groups at 6 months postsurgery (p < 0.01). Aspirin-BMSC treatment has significantly decreased the concentration of TNF-α and IFN-γ (p < 0.05).ConclusionsThe present study shows that BMSC pretreated with aspirin have a greater capacity to repair calvarial bone defects in a mini swine model. The results suggest that the administration of aspirin is capable of improving BMSC-mediated calvarial bone regeneration in a big animal model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0200-4) contains supplementary material, which is available to authorized users.