回复镶嵌现象与隐性营养不良型大疱性表皮松解症治疗的研究进展

Revertant mosaicism and treatment of recessive dystrophic epidermolysis bullosa

隐性营养不良型大疱性表皮松解症是一种遗传性水疱病，由编码Ⅶ型胶原的基因突变引起，对患者生活质量有很大影响，目前治疗多为对症处理，迫切需要更好的治疗方法。近年研究发现，隐性营养不良型大疱性表皮松解症患者存在回复突变所致的片状外观正常皮肤。这种现象称为回复镶嵌现象，也称为天然基因治疗。这一发现开启了回复细胞治疗的可能性，即回复的角质形成细胞体外培养移植到受损皮肤。假如结合患者特异性诱导性多能干细胞方法，可以有机会培养出大片健康皮肤移植物。另外，回复体来源的诱导性多能干细胞还可以分化为造血细胞和间质于细胞，骨髓移植后归巢到水疱区域，即“从皮肤到血细胞，再修复皮肤”。

Recessive dystrophic epidermolysis bullosa （RDEB）, an inherited blistering disease caused by mutations in the gene encoding type VII collagen, has a strong impact on patients＇ quality of life. At present, it is mainly managed by symptomatic treatment, and more effective therapeutic approaches are urgently needed. Recent studies have found the presence of patches of normal-looking skin caused by reverse mutations in patients with RDEB. This phenomenon is called revertant mosaicism, also known as ＂natural gene therapy＂. This finding offers the possibility of revertant cell therapy, namely, transplantation of revertant keratinocytes cultured in vitro onto damaged skin. The combination with patient-specific induced pluripotent stem ceils （iPSCs） makes it possible to harvest large sheets of healthy skin graft. Moreover, iPSCs derived from revertant keratinocytes can differentiate into hematopoietic cells and mesenchymal stem cells, which can home to blistering areas after bone marrow transplantation, namely, ＂from skin to blood ceils, then to repair of skin＂.