Design and development of a soluble PDA-Emodin-PVP-MN patch and its anti-obesity effect in rats.

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

Conversion of carbohydrates into 5-hydroxymethylfurfural catalyzed by ZnCl2 in water.

The incompletely coordinated zinc ions in the concentrated aqueous ZnCl(2) solution catalyze the direct conversion of carbohydrates into 5-hydroxymethylfurfural, and a moderate HMF yield up to 50% can be achieved.

Porcine tooth germ cell conditioned medium can induce odontogenic differentiation of human dental pulp stem cells.

It is suggested that the differentiation of tooth-derived stem cells is modulated by the local microenvironment in which they reside. Previous studies have indicated that tooth germ cell-conditioned medium (TGC-CM) holds the potential to induce dental pulp stem cells (DPSCs) to differentiate into the odontogenic lineage. Nevertheless, human TGC-CM (hTGC-CM) is not feasible in practical application, so we conjectured that xenogenic TGC-CM might exert a similar influence on human dental stem cells. In this study, we chose swine as the xenogenic origin and compared the effect of porcine tooth germ cell-conditioned medium (pTGC-CM) with its human counterpart on human DPSCs. Morphological appearance, colony-forming assay, in vitro multipotential ability, protein and gene expression of the odontogenic phenotype and the in vivo differentiation capacity of DPSCs were evaluated. The results showed that pTGC-CM exerted a similar effect to hTGC-CM in inducing human DPSCs to present odontogenic changes, which were indicated by remarkable morphological changes, higher multipotential capability and the expression of some odontogenic markers in gene and protein levels. Besides, the in vivo results showed that pTGC-CM-treated DPSCs, similar to hTGC-CM-treated DPSCs, could form a more regular dentine-pulp complex. Our data provided the first evidence that pTGC-CM is able to exert almost the same effect on DPSCs with hTGC-CM. The observations suggest that the application of xenogenic TGC-CM may facilitate generating bioengineered teeth from tooth-derived stem cells in future.

Periapical follicle stem cell: a promising candidate for cementum/periodontal ligament regeneration and bio-root engineering.

Mesenchymal stem cell (MSC)-mediated tissue regeneration offers opportunities to regenerate a bio-root and its associated periodontal tissues to restore tooth loss. Previously, we proved that the apical end of developing root was acting as a promising candidate cell source for root/periodontal tissue (R/PT) regeneration. In the present study, we investigated the properties of periapical follicle stem cells (PAFSCs) isolated from the apical end of developing root of human third molars at the root-developing stage and evaluated the potential application of these cells for cementum/periodontal ligament (PDL) regeneration and bio-root engineering. Putative PAFSCs were isolated and subcultured until 20th passage. Cell characteristics of PAFSCs at early or late passage were evaluated and compared with periodontal ligament stem cells (PDLSCs) via a series of histological, cellular, and molecular analyses. PAFSCs at early passage presented crucial stem cell properties and showed a higher proliferation rate than PDLSCs in vitro. Meanwhile, PAFSCs also showed the tissue-regenerative capacity to produce a typical cementum/PDL-like complex in vivo. During long-term passage, both cell populations changed in morphology and gradually lost their stem cell properties. The alkaline phosphatase (ALP) activity and expression of mineralization-related genes markedly declined as more passages were carried out, which might lead to the loss of tissue-regenerative capacity of these 2 groups of cells in vivo. Our findings suggest that developing tissue-derived PAFSCs are a distinctive cell population from PDLSCs and might be a promising candidate for bio-root engineering.

Differentiation of dermal multipotent cells into odontogenic lineage induced by embryonic and neonatal tooth germ cell-conditioned medium.

Stem cell-based therapy represents a novel and more advantageous modality of treatment for tooth defect or loss. However, this strategy is challenged in the circumstances where tooth-derived stem cells are not readily accessible. In present study we sought to explore the possibility of utilizing dermal multipotent cells (DMCs) easily available from skin tissue for odontogenic induction. Using the limiting dilution technique, colony-forming cell population was isolated and characterized by proliferative activity and multilineage differentiation potential. By exposure to conditioned medium of embryonic and neonatal tooth germ cells in culture, the proliferation and mineralization activity of DMCs was elevated, while the embryonic tooth germ cell-conditioned medium (ETGC-CM) produced more significant effects. Meanwhile, ETGC-CM-treated DMCs phenocopied the odontoblasts in vitro as indicated by specific lineage markers. Following in vivo transplantation as cell pellet, ETGC-CM-treated DMCs were capable of producing blocks of mineralized tissues, which resembled those of dental pulp stem cell (DPSC) explants in the same subcutaneous pockets environment. These observations suggest that although more sufficient and continuous inductive microenvironment may be needed for undifferentiated DMCs to perform as odontoblasts, ETGC-CM-treated DMCs indeed acquire properties as those of DPSCs. Our work highlights the potential utility of DMCs as an alternative candidate cell source in hopes of developing more practical strategy of tooth regeneration research and offering promising opportunities for therapeutic approach.

Tissue engineering of cementum/periodontal-ligament complex using a novel three-dimensional pellet cultivation system for human periodontal ligament stem cells.

Limitations of conventional regeneration modalities underscore the necessity of recapitulating development for periodontal tissue engineering. In this study, we proposed a novel three-dimensional pellet cultivation system for periodontal ligament stem cells (PDLSCs) to recreate the biological microenvironment similar to those of a regenerative milieu. Monodispersed human PDLSCs were cultured in medium with ascorbic acid and conditioned medium from developing apical tooth germ cells and were subsequently harvested from culture plate as a contiguous cell sheet with abundant extracellular matrix. The detached cell-matrix membrane spontaneously contracted to produce a single-cell pellet. The PDLSCs embedded within this cell-matrix complex exhibited several phenotypic characteristics of cementoblast lineages, as indicated by upregulated alkaline phosphatase activity, accelerated mineralization, and the expression of bone sialoprotein and osteocalcin genes. When this PDLSC pellets were transplanted into immunocompromised mice, a regular aligned cementum/PDL-like complex was formed. These results suggest that the combination of apical tooth germ cell-conditioned medium and endogenous extracellular matrix could maximally mimic the microenvironment of root/periodontal tissue development and enhance the reconstruction of physiological architecture of a cementum/PDL-like complex in a tissue-mimicking way; on the other hand, such PDLSC pellet may also be a promising alternative to promote periodontal defect repair for future clinical applications.