Establishment of the novel and basic technique for inducing human ES cells to differentiate into connective tissue-type mast cells and their utilization in clinical practice

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In human being, mast cells (MC) play a central role in innate immune and function as cellular mediators of allergy. During infancy, the establishment of innate immuno-system is largely based on the encountering and recognizing of new antigens. Since MCs are typically located at strategically important body barriers, such as skin, vascular and mucosal tissues, they are one of the first reactors in the developmental immunes in infants. However, most of MC data derive solely from experiments in mice and rats. Human MC data are very limited. A particular problem of human MC research is the difficulty in obtaining human material for in vitro studies.I have already established method to generate fuctional MCs from non-human primate ES cells, as reported above. More recently, by the financial supporting from JSPS, we have successfully established a similar method to produce quantitative functionally mature mast cells from hESCs, providing a large variety of possibilities in research on human MC development and their functions. In the present study, I found hESC-derived MC development might be along to two pathpawys : At primary time of induction, they first develop CT-MC that both express chymase and tryptase, and then from multipotential hematopoietic progenitor cells at a comparatively later stage they develop M-MC. This is quite similar to what we have found in monkey ESC-derived MC development, suggesting a unique pathway of MC development during early embryonic/fetal stages is common in human and non-human primates. It also offers a good model to investigate the first establishment of innate immune system mediated by human MCs in infants. Our finding is so far the first report of human/non-human primate ES derived functional MCs in the world, and should open a new research field on MC development.