Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts.
Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts.
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DOI：
10.1038/jid.2013.172
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发表时间：
2013-10
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通讯作者：
K. Tsuchiyama;Shohei Wakao;Yasumasa Kuroda;Fumitaka Ogura;Makoto Nojima;Natsue Sawaya;K. Yamasaki;S. Aiba;M. Dezawa
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文献类型：
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作者：
K. Tsuchiyama;Shohei Wakao;Yasumasa Kuroda;Fumitaka Ogura;Makoto Nojima;Natsue Sawaya;K. Yamasaki;S. Aiba;M. Dezawa
从容易获得的干细胞诱导黑素细胞已经引起了人们对黑素细胞功能障碍治疗的关注。我们发现，多系分化应激耐久（Muse）细胞是人类真皮成纤维细胞中的一种独特的干细胞类型，可以很容易地重新编程为功能性黑素细胞，而其余的成纤维细胞对黑素细胞分化没有贡献。Muse细胞可以作为对阶段特异性胚胎抗原-3（一种未分化的人类胚胎干细胞的标记物）呈阳性的细胞分离出来，并从一个细胞分化成代表所有三个胚层的细胞，同时也是非致瘤性的。使用某些因子组合诱导Muse细胞表达黑素细胞标记物，如酪氨酸酶和小眼相关转录因子，并显示3,4-二羟基- l -苯丙氨酸反应阳性。当Muse细胞衍生的黑色素细胞被纳入三维（3D）培养的皮肤模型时，它们定位于表皮的基底层，并以与真正的黑色素细胞相同的方式产生黑色素。即使将3D培养的皮肤移植到免疫缺陷小鼠身上，它们也能保持黑色素的产生。该技术可能适用于利用Muse细胞从可获得的人成纤维细胞中高效地产生黑素细胞，从而有助于黑素细胞功能障碍的自体移植，如白癜风。
The induction of melanocytes from easily accessible stem cells has attracted attention for the treatment of melanocyte dysfunctions. We found that multilineage-differentiating stress-enduring (Muse) cells, a distinct stem cell type among human dermal fibroblasts, can be readily reprogrammed into functional melanocytes, whereas the remainder of the fibroblasts do not contribute to melanocyte differentiation. Muse cells can be isolated as cells positive for stage-specific embryonic antigen-3, a marker for undifferentiated human embryonic stem cells, and differentiate into cells representative of all three germ layers from a single cell, while also being nontumorigenic. The use of certain combinations of factors induces Muse cells to express melanocyte markers such as tyrosinase and microphthalmia-associated transcription factor and to show positivity for the 3,4-dihydroxy-L-phenylalanine reaction. When Muse cell–derived melanocytes were incorporated into three-dimensional (3D) cultured skin models, they localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. They also maintained their melanin production even after the 3D cultured skin was transplanted to immunodeficient mice. This technique may be applicable to the efficient production of melanocytes from accessible human fibroblasts by using Muse cells, thereby contributing to autologous transplantation for melanocyte dysfunctions, such as vitiligo.