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Adult stem cells from the dermis would be an attractive cell source for therapeutic purposes as well as studying the process of skin aging. Several studies have reported that human dermal stem/progenitor cells (hDSPCs) with multipotent properties exist within the dermis of adult human skin. However, these cells have not been well characterized, because methods for their isolation or enrichment have not yet been optimized. In the present study, we enriched high side scatter (SSC(high))-hDSPCs from normal human dermal fibroblasts using a structural characteristic, intracellular granularity, as a sorting parameter. The SSC(high)-hDSPCs had high in vitro proliferation properties and expressed high levels of SOX2 and S100B, similar to previously identified mouse SOX2+ hair follicle dermal stem cells. The SSC(high)-hDSPCs could differentiate into not only mesodermal cell types, for example, adipocytes, chondrocytes, and osteoblasts, but also neuroectodermal cell types, such as neural cells. In addition, the SSC(high)-hDSPCs exhibited no significant differences in the expression of nestin, vimentin, SNAI2, TWIST1, versican, and CORIN compared with non-hDSPCs. These cells are therefore different from the previously identified multipotent fibroblasts and skin-derived progenitors. In this study, we suggest that hDSPCs can be enriched by using characteristic of their high intracellular granularity, and these SSC(high)-hDSPCs exhibit high in vitro proliferation and differentiation potentials.

Enrichment and Characterization of Human Dermal Stem/Progenitor Cells by Intracellular Granularity