Whitening effect of adipose-derived stem cells: a critical role of TGF-beta 1

Biol Pharm Bull. 2008 Apr;31(4):606-10. doi: 10.1248/bpb.31.606.


It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and exhibit diverse pharmacological actions. The present study examined the unknown pharmacological action of ADSCs regarding whitening effects. A conditioned medium of ADSCs (ADSC-CM) was harvested and the whitening effect of ADSC-CM was studied in melanoma B16 cells. ADSC-CM treatment inhibited the synthesis of melanin and the activity of tyrosinase in a dose dependent manner. To clarify the underlying mechanisms of the whitening action of ADSCs, protein levels of melanogenic proteins were measured by Western blot. Although expressions of microphthalmia-associated transcription factor and tyrosinase-related protein 2 (TRP2) remained unchanged, those of tyrosinase and TRP1 were down-regulated. Transforming growth factor-beta1 (TGF-beta 1), a potent regulator of melanogenic proteins, was neutralized by the addition of a blocking antibody to ADSC-CM, and down-regulated expression of tyrosinase and TRP1 was almost reversed. Collectively, these results indicate that secretary factors of ADSC inhibit melanin synthesis by down-regulating the expression of tyrosinase and TRP1, which are mainly mediated by TGF-beta1.

MeSH terms

  • Blotting, Western
  • Cell Survival
  • Cells, Cultured
  • Color
  • Humans
  • Melanins / biosynthesis*
  • Melanoma, Experimental / metabolism
  • Monophenol Monooxygenase / biosynthesis
  • Monophenol Monooxygenase / metabolism
  • Neutralization Tests
  • Proteomics
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / physiology*
  • Transforming Growth Factor beta1 / physiology*
  • Trypsin
  • Trypsinogen / biosynthesis


  • Melanins
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Trypsinogen
  • Monophenol Monooxygenase
  • PRSS1 protein, human
  • Trypsin