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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: メラノサイト / iPS細胞 / 悪性黒色腫 / 美白物質 / 皮膚色素細胞 / 美白化粧品 / 白斑 / 再生医療 / 脱色素斑 / 白髪

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.

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。

Research Products

• [Journal Article] JCS 2017 Guideline on Management of Vasculitis Syndrome ― Digest Version ― (2020)
  • Author(s): Isobe, M. Amano, K. Arimura, Y. Ishizu, A. Ito, S. Kaname, S. Takahashi, K. Tanemoto, K. Hasegawa, H. Harigai, M. Fujimoto, S. Miyazaki, T. et.al.
  • Journal Title: Circulation Journal Volume: 84 Issue: 2 Pages: 299-359
  • DOI: 10.1253/circj.CJ-19-0773
  • NAID: 130007789906
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-01-24
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Kojic acid alters pheomelanin content in human induced pluripotent stem cell‐derived melanocytes (2020)
  • Author(s): Miyabe Chie、Dong Yupeng、Wakamatsu Kazumasa、Ito Shosuke、Kawakami Tamihiro
  • Journal Title: The Journal of Dermatology Volume: N/A Issue: 4 Pages: 435-436
  • DOI: 10.1111/1346-8138.15260
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Survey of Japanese Dermatological Vasculitis Specialists on Cases of Cutaneous Arteritis (Cutaneous Polyarteritis Nodosa) (2019)
  • Author(s): 川上民裕、有村義宏、池田高治、石黒直子、石津明洋、伊藤吹夕、猪原登志子、沖山奈緒子、小野さち子、鈴木和男、菅原弘二、清島真理子、小寺雅也、田中麻衣子、長谷川稔、古川福実、山口由衣、吉崎歩
  • Journal Title: The Japanese Journal of Dermatology Volume: 129 Issue: 9 Pages: 1901-1907
  • DOI: 10.14924/dermatol.129.1901
  • NAID: 130007694435
  • ISSN: 0021-499X, 1346-8146
  • Year and Date: 2019-08-20
  • Peer Reviewed / Open Access
• [Journal Article] Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody?Associated Vasculitis (2019)
  • Author(s): Masuda Sakiko、Nonokawa Mayu、Futamata Emika、Nishibata Yuka、Iwasaki Sari、Tsuji Takahiro、Hatanaka Yutaka、Nakazawa Daigo、Tanaka Satoshi、Tomaru Utano、Kawakami Tamihiro、Atsumi Tatsuya、Ishizu Akihiro
  • Journal Title: The American Journal of Pathology Volume: 189 Issue: 4 Pages: 839-846
  • DOI: 10.1016/j.ajpath.2019.01.007
  • NAID: 120006820166
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dectin-2?induced CCL2 production in tissue-resident macrophages ignites cardiac arteritis (2019)
  • Author(s): Miyabe Chie、Miyabe Yoshishige、Bricio-Moreno Laura、Lian Jeffrey、Rahimi Rod A.、Miura Noriko N.、Ohno Naohito、Iwakura Yoichiro、Kawakami Tamihiro、Luster Andrew D.
  • Journal Title: Journal of Clinical Investigation Volume: 129 Issue: 9 Pages: 3610-3624
  • DOI: 10.1172/jci123778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sudden elevation of plasma D-dimer levels induced by the combination therapy of dabrafenib and trametinib: Report of two cases. (2019)
  • Author(s): Akino S, Ohashi H, Okano T, Takeuchi S, Kawakami T, Soma Y, Kadono T.
  • Journal Title: Journal of Dermatology Volume: 46 Issue: 4 Pages: 358-360
  • DOI: 10.1111/1346-8138.14798
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Approach for the Derivation of Melanocytes from Induced Pluripotent Stem Cells. (2018)
  • Author(s): Kawakami T, Okano T, Takeuchi S, Osumi K, Soma Y, Itoh M, Hirobe T, Jimbow K.
  • Journal Title: J Invest Dermatol. Volume: 138 Issue: 1 Pages: 150-158
  • DOI: 10.1016/j.jid.2017.07.849
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] テガフール・ギメラシル・オテラシルカリウム配合剤と放射線治療を併用し消退した右口角有棘細胞癌の1例 (2018)
  • Author(s): 森野幸, 大橋洋之, 門野岳史, 松岡摩耶, 川上民裕, 相馬良直
  • Journal Title: 皮膚科の臨床 Volume: 60 Pages: 1275-1278
  • Peer Reviewed
• [Journal Article] Behcet病の治療により増悪した古典型Kaposi肉腫の1例 (2018)
  • Author(s): 奥平あずさ, 門野岳史, 小野田慶子, 森野幸, 松岡摩耶, 川上民裕, 相馬良直, 加藤正樹, 佐藤義典, 山下真幸
  • Journal Title: 皮膚科の臨床 Volume: 60 Pages: 1651-1654
  • Peer Reviewed
• [Journal Article] 腺腔様構造を認めた有棘細胞癌の1例 (2018)
  • Author(s): 久保悠, 門野岳史, 京谷樹子, 太田口里沙子, 竹内そら, 松岡摩耶, 木村聡子, 川上民裕, 相馬良直
  • Journal Title: 皮膚科の臨床 Volume: 60 Pages: 1660-1661
  • Peer Reviewed
• [Journal Article] ヒトiPS細胞由来メラノサイトを使用したオーダーメイド美白化粧品の可能性 (2018)
  • Author(s): 川上民裕
  • Journal Title: Cosmetic Stage Volume: 12 Pages: 14-20
• [Journal Article] Analysis of the effects of all-trans retinoic acid on human melanocytes and melanoblasts in vitro. (2017)
  • Author(s): Kawakami T, Ohgushi A, Hirobe T, Soma Y.
  • Journal Title: J Dermatol. Volume: 44 Issue: 1 Pages: 93-94
  • DOI: 10.1111/1346-8138.13477
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Dectin-2-induced CCL2 production in cardiac macrophages ignites vascular inflammation. (2019)
  • Author(s): Miyabe C, Luster AD, Kawakami T.
  • Organizer: The 118th Annual Meeting of the Japanese Dermatological Association
  • Int'l Joint Research
• [Presentation] Vasculitis and vasculopathy Tamihiro Kawakami, BROWN 2 Diagnostic algorithm for small vessel vasculitis with relation to the new D-CHCC. (2019)
  • Author(s): Kawakami T.
  • Organizer: The 24th World Congress of Dermatology
  • Int'l Joint Research / Invited
• [Presentation] An in vitro established iPS cell-derived human melanocytes as the potential source for melanocyte regeneration. (2019)
  • Author(s): Kawakami T
  • Organizer: The 2nd Meeting of Japanese Society of Vitiligo
  • Int'l Joint Research / Invited
• [Presentation] Dectin-2-induced CCL2 production in cardiac macrophages ignites vascular inflammation. (2019)
  • Author(s): Miyabe C, Miyabe Y, Moreno L, Lian J, Rahimi RA, Miura NN, Ohno N, Iwakura Y, Kawakami T, Luster AD.
  • Organizer: The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Int'l Joint Research
• [Presentation] Evaluation of kojic acid whitening agent using human iPS cell-derived melanocytes. (2019)
  • Author(s): Dong Y, Miyabe C, Ikeda T, Itoh M, Wakamatsu K, Ito S, Hirobe T, Jimbow K, Taguchi K, Tsuda T, Miyashita H, Kawakami T.
  • Organizer: The 29th Japanese Society for Pigment Cell Research Okayama
  • Int'l Joint Research
• [Presentation] Approach for the derivation of melanocytes from induced pluripotent stem (iPS) cells. (2018)
  • Author(s): Kawakami T, Itoh M, Hirobe T, Jimbow K
  • Organizer: International Investigative Dermatology 2018
  • Int'l Joint Research
• [Presentation] イビリムマブにより薬剤性せん妄を来たしその後回復した悪性黒色腫の1例 (2018)
  • Author(s): 下坂玲郁子、松岡摩耶、大橋洋之、大塚陽子、奥平あずさ、久保悠、松浦哲彦、門野岳史、川上民裕、相馬良直
  • Organizer: 第117回日本皮膚科学会総会
• [Presentation] ダーモスコピー上、基底細胞癌との鑑別が困難であった日光角化症の1例 (2018)
  • Author(s): 望月俊彦、川上民裕、門野岳史
  • Organizer: 日本皮膚科学会第879回東京地方会
• [Presentation] 左踵悪性黒色腫に対するペンブロリズマブ投与により急速に出現した腎機能障害にステロイドが奏功した1例 (2018)
  • Author(s): 小野田慶子、大橋洋之、下坂玲郁子、松岡摩耶、門野岳史、川上民裕、相馬良直、小竹徹、寺下真帆
  • Organizer: 第34回日本皮膚悪性腫瘍学会学術大会
• [Presentation] An in vitro established iPS cell-derived human melanocytes as the potential source for the treatment of vitiligo leukoderma. (2018)
  • Author(s): Kawakami T, Itoh M, Hirobe T, Jimbow K.
  • Organizer: The 2nd Annual Meeting of the East Asian Vitiligo Association and the 1st Annual Meeting of the Japanese Society for Vitiligo
  • Int'l Joint Research
• [Presentation] Autologous human melanocytes derived from induced pluripotent stem (iPS) cells and in vivo generation of melanin. (2017)
  • Author(s): Kawakami T, Itoh M, Hirobe T, Jimbow K.
  • Organizer: The XXIII International Pigment Cell Conference (IPCC 2017)
  • Int'l Joint Research / Invited
• [Presentation] ロドデノール白斑が合併したfriction melanosisの1例． (2017)
  • Author(s): 廣川悠季、川上民裕、松岡摩耶、門野岳史、相馬良直.
  • Organizer: 聖マリアンナ医科大学医学会第73回学術集会
• [Presentation] ヒトiPS細胞から高効率・大量・高品質に産生した色素細胞の臨床応用 (2017)
  • Author(s): 川上民裕
  • Organizer: イノベーション・ジャパン2017
• [Presentation] ヒトiPS細胞から高効率・大量・高品質に産生した色素細胞の臨床応用 (2017)
  • Author(s): 川上民裕
  • Organizer: BioJapan2017
• [Patent(Industrial Property Rights)] 高分化度の多能性幹細胞由来細胞の製造方法 (2017)
  • Inventor(s): 川上 民裕
  • Industrial Property Rights Holder: 川上 民裕
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Acquisition Date: 2017