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Hop bitter resins and essential oils are biosynthesized and accumulated in lupulin glands of hop (Humulus lupulus L.). Valerophenone synthase (VPS) is involved in the first steps of biosynthesis of bitter resins, and the VPS gene is specifically expressed in lupulin glands on bracteoles and leaves. In this study, spatial and temporal expression of the VPS gene was studied using in-situ hybridization. No gene signals were observed in the early stage of lupulin gland development, but strong expression was observed when the cuticle was slightly detached from the glandular head cells. Expression levels were remarkably reduced with accumulation of hop bitter resins and essential oils in the sub-cuticular space. The findings suggest that development of lupulin glands is strictly divided into a growth phase and biosyntheticsecretory phase.

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Cell therapy using human-stem-cell-derived pancreatic beta cells (hSC-bs) is a potential treatment method for type 1 diabetes mellitus (T1D). For therapeutic safety, hSC-bs need encapsulation in grafts that are scalable and retrievable. In this study, we developed a lotus-root-shaped cell-encapsulated construct (LENCON) as a graft that can be retrieved after long-term hSC-b transplantation. This graft had six multicores encapsulating hSC-bs located within 1 mm from the edge. It controlled the recipient blood glucose levels for a long-term, following transplantation in immunodeficient diabetic mice. LENCON xenotransplanted into immunocompetent mice exhibited retrievability and maintained the functionality of hSC-bs for over 1 year after transplantation. We believe that LENCON can contribute to the treatment of T1D through long-term transplantation of hSC-bs and in many other forms of cell therapy.

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