NEW APPROACH FOR DERIVATION OF MELANOCYTES FROM INDUCED PLURIPOTENT STEM (iPS) CELLS FOR VITILIGO AND MELANOMA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku Medical and Pharmaceutical University (2018-2019); St. Marianna University School of Medicine (2017)
• Principal Investigator: Kawakami Tamihiro 東北医科薬科大学, 医学部, 教授 (20297659)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: メラノサイト / iPS細胞 / 悪性黒色腫 / 美白物質

Outline of Final Research Achievements

We established human induced pluripotent stem (iPS) cell-derived melanocytes in large quantities within a short period and induced their differentiation and high melanogenic potency. We analyzed the melanin composition in kojic acid treated and untreated control melanocytes using previously reported methods. Kojic acid has a competitive inhibitory effect on monophenolase activity and a mixed inhibitory effect on the diphenolase activity of mushroom tyrosinase. The ability of kojic acid to chelate copper at the active site of the enzyme explains the observed competitive inhibitory effect. The study indicated that treatment with kojic acid downregulates mainly eumelanin production in melanocytes. We demonstrated that kojic acid increases pheomelanin content in melanin produced by iPS cell-derived melanocytes. These results suggest that human iPS cell-derived melanocytes could be used to investigate the mechanism of skin-lightening agents and foods that include kojic acid.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

皮膚生検からメラノサイトを分離し、培養で大量産生されることは困難な技術とされている。白斑の治療でヒトメラノサイトを白斑皮膚に移植するためには、広範囲の皮膚からでないと大量のメラノサイトが獲得できない。メラノサイトが癌化した悪性黒色腫の発症メカニズムは不明である原因の一端に、ヒトメラノサイトの培養が困難が挙げられる。美白化粧品のための成分を開発する際に行われる評価試験で、対象となるヒトメラノサイト株は購入できるが、日本人由来のものがなく白人や黒人由来である。さらにロット毎にメラノサイト株を採取されたヒトが異なる。従って、実験データのばらつきが多い、安定性に掛ける。