Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice
Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice
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DOI：
10.1073/pnas.1000044107
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发表时间：
2010-08-10
影响因子：
11.1
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Fujita, Yasuyuki;Abe, Riichiro;Shimizu, Hiroshi
已经报道了使用骨髓来源的细胞治疗先天性蛋白质缺乏症的尝试。这些努力是基于干细胞可塑性的概念。然而，认为恢复结构蛋白质比恢复分泌酶更困难。本研究旨在阐明骨髓移植（BMT）治疗是否可以挽救由角质形成细胞结构蛋白缺陷引起的大疱性表皮病（EB）。BMT治疗的成年胶原XVII（Col 17）基因敲除小鼠诱导供体来源的角质形成细胞和Col 17的表达与半桥粒结构的恢复和更好的皮肤表现，以及提高生存率。造血干细胞和间充质干细胞在BMT治疗模型中都有产生Col 17的潜力。此外，人脐带血CD 34（+）细胞也分化成角质形成细胞，并在移植的免疫功能低下（NOD/SCID/gamma（null）（c））小鼠中表达人皮肤成分蛋白。目前常规的BMT技术作为治疗人EB的系统性治疗方法具有显著的潜力。
Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. However, it is considered more difficult to restore structural proteins than to restore secretory enzymes. This study aims to clarify whether bone marrow transplantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) knockout mice induced donor-derived keratinocytes and Col17 expression associated with the recovery of hemidesmosomal structure and better skin manifestations, as well improving the survival rate. Both hematopoietic and mesenchymal stem cells have the potential to produce Col17 in the BMT treatment model. Furthermore, human cord blood CD34(+) cells also differentiated into keratinocytes and expressed human skin component proteins in transplanted immunocompromised (NOD/SCID/gamma(null)(c)) mice. The current conventional BMT techniques have significant potential as a systemic therapeutic approach for the treatment of human EB.