Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa
Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa
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DOI：
10.1016/j.jid.2019.03.1155
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发表时间：
2019-10-01
影响因子：
6.5
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Matsumura, Wakana;Fujita, Yasuyuki;Shimizu, Hiroshi
最近有报道称，遗传性皮肤病有零星的看起来正常的区域，其中部分角质形成细胞已从致病基因突变（逆转镶嵌）中恢复。我们观察了一例隐性营养不良大疱性表皮松解症用培养的自体表皮移植物（CEAs）治疗，其自体表皮移植物在16年内保持上皮。我们证明了CEA产物和嫁接区域包含有反向嵌合的细胞。基于这些发现，我们进行了一项由研究者发起的临床试验，从临床逆转皮肤中提取cea治疗隐性营养不良大疱性表皮松解症。通过遗传分析、免疫荧光、电子显微镜和深度测序定量分析供体位点。主要终点是最后一次CEA应用后4周每位患者的溃疡上皮率。3例隐性营养不良大疱性表皮松解伴8个溃疡患者入组，每个患者在主要终点的上皮化率分别为87.7%、100%和57.0%。发现CEA移植后的临床效果持续至少76周。3例患者中有1例在供体皮肤和移植后区域有明显的逆转嵌合现象。来自临床正常皮肤的cea是一种潜在的耐受性良好的治疗隐性营养不良大疱性表皮松解症的方法。
Inherited skin disorders have been reported recently to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism). We observed a case of recessive dystrophic epidermolysis bullosa treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with revertant mosaicism. Based on these findings, we conducted an investigator-initiated clinical trial of CEAs from clinically revertant skin for recessive dystrophic epidermolysis bullosa. The donor sites were analyzed by genetic analysis, immunofluorescence, electron microscopy, and quantification of the reverted mRNA with deep sequencing. The primary endpoint was the ulcer epithelization rate per patient at 4 weeks after the last CEA application. Three patients with recessive dystrophic epidermolysis bullosa with 8 ulcers were enrolled, and the epithelization rate for each patient at the primary endpoint was 87.7%, 100%, and 57.0%, respectively. The clinical effects were found to persist for at least 76 weeks after CEA transplantation. One of the three patients had apparent revertant mosaicism in the donor skin and in the post-transplanted area. CEAs from clinically normal skin are a potentially well-tolerated treatment for recessive dystrophic epidermolysis bullosa.