Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors

J Dermatol Sci. 2009 Feb;53(2):96-102. doi: 10.1016/j.jdermsci.2008.08.007. Epub 2008 Oct 1.


Background: Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin via secretion of growth factors and activation of dermal fibroblasts.

Objective: Paracrine mechanism reducing ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study.

Methods and results: Wrinkles were induced by an eight-week UVB irradiation, and were significantly improved by the subcutaneous injection of ADSC in hairless mice. In a replica analysis, parameters involving wrinkles were improved with mid-level and high doses of ADSC (1x10(4) and 1x10(5) cells). Dermal thickness and collagen contents in the dermis also were increased in the ADSC-injected groups. To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM in a dose-dependent manner. In a cell cycle analysis, ADSC-CM decreased the UVB-induced apoptotic cell death, which was demonstrated by the reduced sub-G1 phase of HDF. In addition, the ADSC-CM increased the protein expression of collagen type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for the increased collagen contents in the dermis.

Conclusions: Collectively, these results indicate that the ADSC and its secretory factors are effective for UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and stimulating collagen synthesis of HDF.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Proliferation
  • Cells, Cultured
  • Collagen Type I / metabolism
  • Culture Media, Conditioned / metabolism
  • Dermis / metabolism
  • Dermis / pathology
  • Dermis / radiation effects
  • Dermis / surgery*
  • Female
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / radiation effects
  • Humans
  • Matrix Metalloproteinase 1 / metabolism
  • Mice
  • Mice, Hairless
  • Models, Animal
  • Paracrine Communication*
  • Skin Aging* / pathology
  • Stem Cell Transplantation*
  • Stem Cells / metabolism*
  • Subcutaneous Fat / metabolism*
  • Ultraviolet Rays


  • Collagen Type I
  • Culture Media, Conditioned
  • MMP1 protein, human
  • Matrix Metalloproteinase 1