Currently, there is no definitive treatment for lymphatic disorders. Adipose-derived stem cells (ADSCs) have been reported to promote lymphatic regeneration in lymphedema models, but the mechanisms underlying the therapeutic effects remain unclear. Here, we tested the therapeutic effects of ADSC transplantation on lymphedema using a secondary lymphedema mouse model. The model was established in C57BL/6J mice by x-irradiation and surgical removal of the lymphatic system in situ. The number of lymphatic vessels with anti-lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunoreactivity increased significantly in mice subjected to transplantation of 7.5 × 105 ADSCs. X-irradiation suppressed lymphatic vessel dilation, which ADSC transplantation could mitigate. Proliferative cell nuclear antigen staining showed increased lymphatic endothelial cell (LEC) and extracellular matrix proliferation. Picrosirius red staining revealed normal collagen fiber orientation in the dermal tissue after ADSC transplantation. These therapeutic effects were not related to vascular endothelial growth factor (VEGF)-C expression. Scanning electron microscopy revealed structures similar to the intraluminal pillar during intussusceptive angiogenesis on the inside of dilated lymphatic vessels. We predicted that intussusceptive lymphangiogenesis occurred in lymphedema. Our findings indicate that ADSC transplantation contributes to lymphedema reduction by promoting LEC proliferation, improving fibrosis and dilation capacity of lymphatic vessels, and increasing the number of lymphatic vessels via intussusceptive lymphangiogenesis.

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Shrimp is a causative food that elicits food-dependent exercise-induced anaphylaxis (FDEIA). In this study, we sought to identify IgE-binding allergens in patients with shrimp-FDEIA. Sera were obtained from eight patients with shrimp-FDEIA and two healthy control subjects. Proteins were extracted from four shrimp species by homogenization in Tris buffer. Immunoblot analysis revealed that IgE from patient sera bound strongly to a 70-kDa and a 43-kDa protein in a preparation of Tris-soluble extracts from Litopenaeus vannamei. Mass spectrometry identified the 70-kDa and 43-kDa proteins as a P75 homologue and fructose 1,6-bisphosphate aldolase (FBPA), respectively. To confirm that the putative shrimp allergens were specifically recognized by serum IgE from shrimp-FDEIA patients, the two proteins were purified by ammonium sulfate precipitation followed by reversed-phase HPLC and/or anion-exchange hydrophobic interaction chromatography and then subjected to immunoblot analysis. Purified P75 homologue and FBPA were positively bound by serum IgE from one and three, respectively, of the eight patients with shrimp-FDEIA, but not by sera from control subjects. Thus, P75 homologue and FBPA are identified as IgE-binding allergens for shrimp-FDEIA. These findings could be useful for the development of diagnostic tools and desensitization therapy for shrimp-FDEIA patients.

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Secondary lymphedema is a common complication of lymph node dissection or radiation therapy for cancer treatment. Conventional therapies such as compression sleeve therapy, complete decongestive physiotherapy, and surgical therapies decrease edema; however, they are not curative because they cannot modulate the pathophysiology of lymphedema. Recent advances reveal that the activation and accumulation of CD4+ T cells are key in the development of lymphedema. Based on this pathophysiology, the efficacy of pharmacotherapy (tacrolimus, anti-IL-4/IL-13 antibody, or fingolimod) and cell-based therapy for lymphedema has been demonstrated in animal models and pilot studies. In addition, mesenchymal stem/stromal cells (MSCs) have attracted attention as candidates for cell-based lymphedema therapy because they improve symptoms and decrease edema volume in the long term with no serious adverse effects in pilot studies. Furthermore, MSC transplantation promotes functional lymphatic regeneration and improves the microenvironment in animal models. In this review, we focus on inflammatory cells involved in the pathogenesis of lymphedema and discuss the efficacy and challenges of pharmacotherapy and cell-based therapies for lymphedema.

Skin wounds often repair themselves completely over time; however, this is true only for healthy individuals. Although various studies are being conducted to improve wound-healing therapy outcomes, the mechanisms of wound healing and regeneration are not completely understood yet. In recent years, mesenchymal stem cells (MSCs) have been reported to contribute significantly to wound healing and regeneration. Understanding the function of MSCs will help to elucidate the fundamentals of wound healing. MSCs are multipotent stem cells that are used in regenerative medicine for their ability to self-renew and differentiate into bone, fat, and cartilage, with few ethical problems associated with cell harvesting. Additionally, they have anti-inflammatory and immunomodulatory properties and antifibrotic effects via paracrine signaling, and many studies have been conducted to use them to treat graft-versus-host disease, inflammatory bowel disease, and intractable cutaneous wounds. Many substances derived from MSCs are involved in the wound-healing process, and specific cascades and pathways have been elucidated. This review aims to explain the fundamental role of MSCs in wound healing and the effects of MSCs on fibroblasts.

CaF2 nanostructures were synthesized from Ca-silicide powders by a diluted aqueous HF treatment. Commercially-available CaSi2 crystal powders and calcium silicide powders prepared by mechanical alloying were used as the source materials, and CaF2 nanosheet bundles and nanobunches of the CaF2 nanoparticles were obtained, respectively. The morphological property of the resulting CaF2 nanostructures was characterized by electron microscopy. It was found that the morphology of the resulting products depended on the starting materials. In addition, the growth mechanism of the CaF2 nanostructures was discussed from a topological synthesis point of view.

The early ingestion of food can prevent the onset of food allergy related to inducing oral tolerance (OT). We developed the Hokushin wheat line as a hypoallergenic wheat (1BS-18H) lacking ω5-gliadin, a major allergen of wheat-dependent exercise-induced anaphylaxis (WDEIA). The 1BS-18H wheat had lower ability of sensitization for ω5-gliadin compared with Hokushin wheat. Here, we evaluated the induction of OT to gluten and ω5-gliadin by the early consecutive ingestion of 1BS-18H gluten using a rat model of wheat allergy. Rats were subcutaneously immunized with commercial gluten or native ω5-gliadin following the daily oral administration of gluten. The daily oral administration of 1BS-18H gluten for 5 days before immunization suppressed the increase in gluten- or ω5-gliadin-specific IgE and IgG1 antibodies induced by immunization to a level similar to Hokushin gluten. Intravenous challenge with gluten or ω5-gliadin did not decrease the rectal temperature in rats with OT induced by 1BS-18H or Hokushin gluten, although it was decreased in non-OT rats. In conclusion, the early consecutive ingestion of 1BS-18H wheat before sensitization induced OT to gluten and ω5-gliadin. These findings support the benefit of 1BS-18H wheat to prevent wheat allergy including WDEIA by consecutive ingestion in humans.