Elucidation of significance of derangement of cell differentiation in metabolic syndrome ("cell mapping) and development of cell re-differentiation therapy using human ES cells

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This project was conducted to delineate the cell differentiation pathways involved in the pathogenesis of metabolic syndrome, that is, the differentiation pathway of mesenchymal cells ; vascular cells (endothelial cells and vascular smooth muscle cells), adipocytes and skeletal muscle cells, and examined the possibility of the re-differentiation therapy for metabolic syndrome, using human ES cells.We established the culture methods to differentiate vascular cells, osteocytes/chondrocytes and adipocytes, using human ES cells and traced the cell surface marker expressions in these cells. Adrenomedullin (AM), the vasodilator hormones, was shown to augment endothelial differentiation of human ES cell-derived vascular progenitor cells (VPC). AM was further demonstrated to induce arterialization of ES cell-derived endothelial cells through Notch signaling pathway. We also reported that AM was expressed highly in adipocytes and co-culture of adipocytes and ES cell-derived VPC resulted in endothelial cell differentiation.