Klotho enhances bone regenerative function of hPDLSCs via modulating immunoregulatory function and cell autophagy.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) have a superior ability to promote the formation of new bones and achieve tissue regeneration. However, mesenchymal stem cells (MSCs) are placed in harsh environments after transplantation, and the hostile microenvironment reduces their stemness and hinders their therapeutic effects. Klotho is an antiaging protein that participates in the regulation of stress resistance. In our previous study, we demonstrated the protective ability of Klotho in hPDLSCs. METHODS: A cranial bone defect model of rats was constructed, and the hPDLSCs with or without Klotho pretreatment were transplanted into the defects. Histochemical staining and micro-computed tomography were used to detect cell survival, osteogenesis, and immunoregulatory effects of hPDLSCs after transplantation. The in vitro capacity of hPDLSCs was measured by a macrophage polarization test and the inflammatory level of macrophages. Furthermore, we explored autophagy activity in hPDLSCs, which may be affected by Klotho to regulate cell homeostasis. RESULTS: Pretreatment with the recombinant human Klotho protein improved cell survival after hPDLSC transplantation and enhanced their ability to promote bone regeneration. Furthermore, Klotho pretreatment can promote stem cell immunomodulatory effects in macrophages and modulate cell autophagy activity, in vivo and in vitro. CONCLUSION: These findings suggest that the Klotho protein protects hPDLSCs from stress after transplantation to maintain stem cell function via enhancing the immunomodulatory ability of hPDLSCs and inhibiting cell autophagy.

SHED-derived exosomes promote LPS-induced wound healing with less itching by stimulating macrophage autophagy.

High-quality cutaneous wound healing is associated with rapid wound closure and a comfortable healing process. Currently, exosomes derived from mesenchymal stem cells displayed a prominent therapeutic effect on skin wound closure. But the therapeutic approaches for wound itching are very limited in clinical. Stem cells from human exfoliated deciduous teeth (SHED) may offer a unique exosome resource for cell-free therapeutics in potential clinical applications. Here, we investigated the common mechanisms underlying wound closure and unpleasant sensation of itching, focusing on the contribution of the SHED-derived exosome to immune response and wound itching during healing. The effects of SHED-derived exosomes on inflammatory wound healing were examined using lipopolysaccharide (LPS)-induced wounds in a mouse model. We found prolonged inflammation and distinct itch responses in skin wound tissue during LPS-induced wound healing. SHED-derived exosomes facilitated LPS-induced wound closure and relieved wound itching. Therefore, they are ideal for the treatment of wound healing. Macrophages in skin wound tissues are responsible for autophagy during wound healing. Macrophage autophagy also regulates cell proliferation, migration, and neuronal signal transduction in vitro. SHED-derived exosomes containing miR-1246 enhanced autophagy by regulating macrophage function through the AKT, ERK1/2, and STAT3 signaling pathways. Thus, SHED-derived exosomes promote wound healing with less itching in an LPS-induced wound model by stimulating macrophage autophagy, which has implications for the treatment of inflammatory wound healing.

A novel cutting machine supports dental students to study the histology of the tooth hard tissue.

BACKGROUND/PURPOSE: Ground section is the only way to study tooth enamel, and the conventional methods of making ground sections, grinding by hand or using a hard tissue microtome are either too time consuming or money costing. This study aimed to develop and assess a novel cutting machine in making ground sections and learning aid for dental students. MATERIALS AND METHODS: By using the novel cutting machine, the students cut the embedding teeth and got 50 µm ground sections efficiently. A series of fine/coarse combination stones were used for grinding the sections to uniform 20 µm thickness. Self-made ground sections were used in the lab class of tooth tissue. Questionnaires were designed to assess the participants' attitude towards the cutting machine and their knowledge of the tooth tissue before and after making the tooth ground sections. RESULTS: Our findings indicated that the novel cutting machine can act as an efficient tool to make tooth ground sections. Indeed, data indicated that making tooth ground section progress can assist students' understanding of the structure and function of tooth and their pathology knowledge had improved. From a qualitative point of view, the students described making tooth ground section progress improve their practical ability and study interest in oral pathology. CONCLUSION: Overall, these findings indicate that our novel cutting machine can act as an efficient tool to make tooth ground sections and support dental students to study the pathology of the tooth hard tissue in a simple and functional way.