In this study, we investigated the possibility of using local administration of allogeneic bone marrow mesenchymal stem cells (BMMSCs) to induce tissue regeneration in periodontal defects in a rat model of periodontitis. BMMSCs isolated from rats were mixed with 0.9% NaCl solution and injected into periodontal defects. Control groups were 0.9% NaCl solution or left untreated. The clinical assessments, x-rays, and histological examinations were used to evaluate the effect. At 12 wks post-transplantation, quantitative analysis revealed average probing bone loss values of 1.2 ± 0.19, 1.6 ± 0.2, and 1.7 ± 0.14; the bone regeneration rate was 53%, 45%, and 44% in the BMMSC+NaCl group, NaCl group, and untreated group, respectively. The clinical assessments, x-rays, and histological examinations revealed significant periodontal tissue regeneration in the BMMSC injection group, compared with the control groups. The ELISA results showed that TNFα, IFNγ, and IL1β were 2,674.88 ± 102.77 pg/mL vs. 3,422.1 ± 51.98 pg/mL, 609.85 ± 25.5 pg/mL vs. 803.79 ± 33.85 pg/mL, and 1,038.46 ± 76.29 pg/mL vs. 1,175.26 ± 105.55 pg/mL in the BMMSC+NaCl group and NaCl group, respectively, indicating that BMMSC injection inhibited the inflammatory factors TNFα, IFNγ, and IL1β. Our results indicate that local administration of BMMSCs can repair defects due to periodontitis, exerting anti-inflammatory and immunomodulatory functions.

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed.

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Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSC differentiation. Here, we investigated FBXL11, a histone demethylase, lysine (K)-specific demethylase 2A, which is evolutionarily conserved, ubiquitously expressed, and a member of the JmjC-domain-containing histone demethylase family. We tested whether FBXL11 could inhibit the osteo/dentinogenic differentiation potential in MSC cells with gain-and loss-of-function assays. We found that FBXL11 regulated osteo/dentinogenic differentiation in MSC cells. Furthermore, we found that the gene encoding the epidermal growth factor, Epiregulin (EREG), was a downstream target of FBXL11, and that EREG mediated FBXL11 regulation of MSC differentiation. Moreover, we found that the FBXL11 histone demethylase function was activated by associating with BCL6 corepressor, and this complex could repress EREG transcription by increasing histone K4/36 methylation in the EREG promoter. In conclusion, our results elucidated a new function for FBXL11 and EREG, explored the molecular mechanism underlying directed differentiation in MSC cells, and identified potential target genes for improving tissue regeneration techniques. STEM CELLS 2013;31:126-136 Disclosure of potential conflicts of interest is found at the end of this article.

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