Abstract
Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs) with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM) collected from hDSPC cultures (hDSPC-CM) exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated β-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin.
Highlights
Normal somatic cells cultured in vitro display a limited capacity to divide, and eventually become senescent [1]
We previously demonstrated that collagen type IV-enriched human dermal stem/progenitor cells exhibit stem cell-like characteristics [17]
We found that human dermal stem/progenitor cells (hDSPCs)-conditioned medium (CM) significantly decreased SA-β-gal production, p53 phosphorylation, and the expression level of p21, all of which were generally increased in senescent fibroblasts (Figure 2)
Summary
Normal somatic cells cultured in vitro display a limited capacity to divide, and eventually become senescent [1]. Adult stem cells are indispensable for maintaining homeostasis in all tissues of the body Representative characteristics of these stem cells are their self-renewal and multipotent capacities [7,8,9,10,11,12,13,14,15,16,17,18]. We found that hDSPC-CM significantly increased proliferation, and reduced SA-β-gal expression, p53 phosphorylation, and reactive oxygen species (ROS) levels in senescent fibroblasts These data suggest that hDSPC-CM is a potential stem cell-based therapeutic agent to prevent aging in the skin
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