Human Adipose Mesenchymal Cells Inhibit Melanocyte Differentiation and the Pigmentation of Human Skin via Increased Expression of TGF-β1

J Invest Dermatol. 2017 Dec;137(12):2560-2569. doi: 10.1016/j.jid.2017.06.027. Epub 2017 Jul 31.


There is accumulating evidence that interactions between epidermal melanocytes and stromal cells play an important role in the regulation of skin pigmentation. In this study we established a pigmented dermo-epidermal skin model, melDESS, of human origin to investigate the effects of distinct stromal cells on melanogenesis. melDESS is a complex, clinically relevant skin equivalent composed of an epidermis containing both melanocytes and keratinocytes. Its dermal compartment consists either of adipose tissue-derived stromal cells, dermal fibroblasts (Fbs), or a mixture of both cell types. These skin substitutes were transplanted for 5 weeks on the backs of immuno-incompetent rats and analyzed. Gene expression and Western blot analyses showed a significantly higher expression of transforming growth factor-β1 by adipose tissue-derived stromal cells compared with dermal Fbs. In addition, we showed that melanocytes responded to the increased levels of transforming growth factor-β1 by down-regulating the expression of key melanogenic enzymes such as tyrosinase. This caused decreased melanin synthesis and, consequently, greatly reduced pigmentation of melDESS. The conclusions are of utmost clinical relevance, namely that adipose tissue-derived stromal cells derived from the hypodermis fail to appropriately interact with epidermal melanocytes, thus preventing the sustainable restoration of the patient's native skin color in bioengineered skin grafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Proliferation
  • Epidermis / metabolism
  • Female
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Humans
  • Male
  • Melanocytes / cytology*
  • Middle Aged
  • Pigmentation*
  • Rats
  • Rats, Nude
  • SOX9 Transcription Factor / metabolism
  • Skin / metabolism*
  • Skin, Artificial
  • Stromal Cells / cytology
  • Tissue Engineering
  • Transforming Growth Factor beta1 / metabolism*
  • Young Adult


  • SOX9 Transcription Factor
  • SOX9 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta1