The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.
Mature neurons polarize by extending an axon and dendrites. In vitro studies of dissociated neurons have demonstrated that axons are initiated from a nonpolarized stage. Dissociated hippocampal neurons form four to five minor neurites shortly after plating but then one of them starts to elongate rapidly to become the future axon, whereas the rest constitutes the dendrites at later stages. However, neuroepithelial cells as well as migrating neurons in vivo are already polarized, raising the possibility that mature neurons inherit the polarities of immature neurons of neuroepithelial or migrating neurons. Here we show that the axon of interneurons in mouse cortical explant emerges from a morphologically nonpolarized shape. The morphological maturation of cortical interneurons labeled by electroporation at an embryonic stage was analyzed by time-lapse imaging during the perinatal stage. In contrast to earlier stages, most interneurons at this stage show sea urchin-like nonpolarized shapes with alternately extending and retracting short processes. Abruptly, one of these processes extends to give rise to an outstandingly long axon-like process. Given that the interneurons exhibit typical polarized shapes during embryonic development, the present results suggest that axon-dendrite polarity develops from a nonpolarized intermediate stage.
Anionic surfactants are often used for cleaning and pharmaceutical purposes because of their strong surfactancy and foaming property. However, they are rarely ingested orally, the skin is a part of the human body most affected by surfactants. Barrier function of the skin is very strong, but the anionic surfactants can cause serious damages to it. Recently, amino acid-based surfactants have attracted attention as a safer option owing to their biocompatibility. Cytotoxicity examinations revealed that the amino acid-based surfactants are superior to sulfate-based surfactants. However, a systematical and comprehensive study related to the effect of these surfactants on skin barrier function has not yet been reported. In this work, skin permeation test using the skin of hairless mice and HPLC method is carried out. The material transmission speed through skin in a steady state was different between each surfactant treatment. We performed a comprehensive analysis of the effect of surfactants on skin barrier function and defined Transmission Index as an index for the degree of effect of surfactants. Glutamate series amino acid-based surfactant were effective to Transmission Index and we guessed the cause was due to adsorption. Based on the finding this study, we suggest using adsorptive property as a measure to the effect on the skin barrier function.
Cutaneous larva migrans (CLM) is characterized as creeping eruption/serpiginous erythema and/or mobile erythematous induration on the skin. In Japan, Gnathostoma spp. are the most well known pathogens causing CLM, especially the creeping eruption type. Recently, Spirurina type X larvae have been added to the list of causative agents for creeping eruption in Japan. Here we report one confirmed and 6 suspected cases of creeping eruption caused by infection with dog hookworm larvae. The patients were assumed to have been infected overseas. Dog hookworms such as Ancylostoma caninum and A. brasiliense should be considered as possible causative agents for creeping eruption, especially when the patients have a history of travelling overseas.
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