Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa.
Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa.
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DOI：
10.1038/jid.2010.346
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发表时间：
2011-04
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影响因子：
--
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中科院分区：
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--
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隐性营养不良性大疱性表皮松解症 (RDEB) 是一种遗传性水疱性皮肤病，由编码 VII 型胶原 (Col7) 的 COL7A1 基因突变引起，Col7 是真皮-表皮交界处锚定原纤维的主要成分。患有 RDEB 的个体会出现疼痛的水疱和粘膜糜烂，目前没有有效的治疗方法。尽管如此，患者治疗方面正在取得一些进展，并且基于间充质细胞和造血细胞的细胞疗法在早期临床试验中已显示出希望。为了建立个性化、基因校正、患者特异性细胞转移的基础，我们从三名 RDEB 受试者（RDEB iPS 细胞）中产生了诱导多能干细胞。我们发现干细胞更新不需要 Col7，并且 RDEB iPS 细胞可以分化为造血和非造血谱系。与 RDEB 成纤维细胞和角质形成细胞去分化为 RDEB iPS 细胞相关的特定表观遗传谱与在野生型 iPS 细胞中观察到的相似。重要的是，人类野生型和 RDEB iPS 细胞在体内分化成类似皮肤的结构。基因校正的 RDEB iPS 细胞表达 Col7。这些数据确定了 RDEB iPS 细胞产生自体造血移植物和皮肤细胞的潜力，这些细胞具有治疗这种遗传性皮肤病典型的皮肤和粘膜糜烂的固有能力。
Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited blistering skin disorder caused by mutations in the COL7A1 gene-encoding type VII collagen (Col7), the major component of anchoring fibrils at the dermal-epidermal junction. Individuals with RDEB develop painful blisters and mucosal erosions, and currently there are no effective forms of therapy. Nevertheless, some advances in patient therapy are being made, and cell-based therapies with mesenchymal and hematopoietic cells have shown promise in early clinical trials. To establish a foundation for personalized, gene-corrected, patient-specific cell transfer, we generated induced pluripotent stem cells from three subjects with RDEB (RDEB iPS cells). We found that Col7 was not required for stem cell renewal and that RDEB iPS cells could be differentiated to both hematopoietic and non-hematopoietic lineages. The specific epigenetic profile associated with de-differentiation of RDEB fibroblasts and keratinocytes into RDEB iPS cells was similar to that observed in wild-type iPS cells. Importantly, human wild-type and RDEB iPS cells differentiated in vivo into structures resembling skin. Gene-corrected RDEB iPS cells expressed Col7. These data identify the potential of RDEB iPS cells to generate autologous hematopoietic grafts and skin cells with the inherent capacity to treat the skin and mucosal erosions that typify this genodermatosis.
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