Generation of functional multipotent keratinocytes from mouse induced pluripotent stem cells.
Generation of functional multipotent keratinocytes from mouse induced pluripotent stem cells.
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DOI：
10.1007/978-1-62703-227-8_22
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发表时间：
2013-01-01
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影响因子：
--
通讯作者：
Roop, Dennis R
中科院分区：
文献类型：
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作者：
Bilousova, Ganna;Roop, Dennis R
体细胞重编程为诱导多能干细胞（iPSC）的最新进展提供了开发用于治疗各种疾病（包括遗传性皮肤病）的新治疗方法的可能性。虽然最终目标是使用iPSC治疗人类疾病，但在将iPSC技术引入临床之前，仍需要对临床前小鼠模型进行广泛的研究。因此，从小鼠iPSC衍生多能角质形成细胞的方法是特别重要的，因为它可以允许使用模拟这些疾病的小鼠模型评估使用iPSC治疗遗传性皮肤病的可行性。在这里，我们描述了两种替代方案，用于将小鼠iPSC有效分化为功能性角质形成细胞，当移植到小鼠上时，这些细胞能够重建正常的分层表皮、毛囊和皮脂腺。根据研究中使用的小鼠遗传背景，每种方案导致角质形成细胞衍生的不同产率和效率。这两种方案都采用了视黄酸和骨形态发生蛋白-4的应用，并在胶原IV型包被的培养皿上生长，以诱导iPSC向角质形成细胞谱系分化。
Recent advances in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) offer the possibility of developing new therapeutic approaches for the treatment of a variety of diseases, including inherited skin disorders. While the ultimate goal is the use of iPSCs in the treatment of human diseases, extensive research is still required with preclinical mouse models before iPSC technology can be introduced into the clinic. Therefore, the methodology for the derivation of multipotent keratinocytes from mouse iPSCs is of particular importance since it may allow for the assessment of the feasibility of using iPSCs in the treatment of inherited skin disorders using mouse models which mimic these diseases. Here, we describe two alternative protocols for the efficient differentiation of mouse iPSCs into functional keratinocytes capable of reconstituting a normal stratified epidermis, hair follicles, and sebaceous glands when grafted onto mice. Each protocol results in a different yield and efficiency of keratinocyte derivation depending on the mouse genetic background used in the study. Both protocols employ applications of retinoic acid and bone-morphogenetic protein-4 and growth on collagen type IV-coated dishes to induce iPSC differentiation toward a keratinocyte lineage.