Abstract
It is still unknown whether the human interfollicular epidermis harbors a reservoir of melanocyte precursor cells. Here, we clearly distinguish between three distinct types of melanocytes in human interfollicular epidermis: (1) cKit+CD90-, (2) cKit+CD90+, and (3) cKit-CD90+. Importantly, we identify the Kit tyrosine kinase receptor (cKit) as a marker expressed specifically in mature, melanin-producing melanocytes. Thus, both cKit+CD90- and cKit+CD90+ cells represent polydendritic, pigmented mature melanocytes, whereas cKit-CD90+ cells display bipolar, non-dendritic morphology with reduced melanin content. Additionally, using tissue-engineered pigmented dermo-epidermal skin substitutes (melDESSs), we reveal that the cKit expression also plays an important role during melanogenesis in melDESS in vivo. Interestingly, cKit-CD90+ cells lack the expression of markers such as HMB45, TYR, and TRP1 in vitro and in vivo. However, they co-express neural-crest progenitor markers and demonstrate multilineage differentiation potential in vitro. Hence, we propose that cKit-CD90+ cells constitute the precursor melanocyte reservoir in human interfollicular epidermis.
Keywords: dermo-epidermal skin substitutes; human epidermis; mature melanocytes; melanin synthesis; melanocyte stem cells; neural-crest progenitor cells; skin pigmentation; tissue engineering.