Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Adv Exp Med Biol. 2018;1103:255-271. doi: 10.1007/978-4-431-56847-6_14.
The skin composes physiological and chemical barrier and renews skin component cells throughout the human life. Melanocytes locate in the basal layer of the epidermis and produce melanin to protect the skin from ultraviolet. Melanin plays key roles in determining human skin and hair color. Melanocyte dysfunction observed in albinism and vitiligo not only causes cosmetic problems but also increases risk of skin cancer. As rejuvenate therapy, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to generate melanocytes. Other than ES and iPS cells, human skin tissues maintain pluripotent stem cells, named multilineage-differentiating stress-enduring (Muse) cells. We employ Muse cells isolated from human fibroblasts and adipose tissue to differentiate into melanocytes (Muse-MC). Muse-MC express melanocyte-related molecules, such as tyrosinase and DCT, and show tyrosinase activity. We also succeeded to differentiate Muse cells into fibroblasts and keratinocytes and created three-dimensional (3D) reconstituted skin with Muse cell-derived melanocytes, fibroblasts, and keratinocytes. The 3D reconstituted skin of Muse cell-derived cells coordinately showed epidermis layers and Muse-MC localized in the basal layer of the epidermis. Thus Muse cells in the human skin can be a source of rejuvenation medicine for the skin reconstruction.
皮肤构成生理和化学屏障，并在人类的一生中不断更新皮肤成分细胞。黑素细胞位于表皮的基底层，产生黑色素以保护皮肤免受紫外线伤害。黑色素在决定人类皮肤和头发颜色方面起着关键作用。白化病和白癜风中观察到的黑素细胞功能障碍不仅导致美容问题，还增加了皮肤癌的风险。作为再生疗法，胚胎干细胞 (ES) 和诱导多能干细胞 (iPS) 已被报道可产生黑素细胞。除了 ES 和 iPS 细胞外，人类皮肤组织还维持着多能干细胞，称为多能性分化应激耐受 (Muse) 细胞。我们从人成纤维细胞和脂肪组织中分离出 Muse 细胞，并将其分化为黑素细胞 (Muse-MC)。Muse-MC 表达黑素细胞相关分子，如酪氨酸酶和 DCT，并表现出酪氨酸酶活性。我们还成功地将 Muse 细胞分化为成纤维细胞和角质形成细胞，并利用 Muse 细胞衍生的黑素细胞、成纤维细胞和角质形成细胞创建了三维 (3D) 重组皮肤。Muse 细胞衍生细胞的 3D 重组皮肤协调地显示出表皮层，并且 Muse-MC 位于表皮的基底层。因此，人类皮肤中的 Muse 细胞可以成为皮肤重建的再生医学的来源。
