Bondanza Sergio, Bellini Melissa, Roversi Gaia, Raskovic Desanka, Maurelli Riccardo, Paionni Emanuel, Paterna Patrizia, Dellambra Elena, Larizza Lidia, Guerra Liliana
Laboratory of Tissue Engineering and Cutaneous Physiopathology, Istituto Dermopatico dell'Immacolata, IRCCS, Via dei Monti di Creta 104, Rome, Italy.
J Invest Dermatol. 2007 Mar;127(3):676-86. doi: 10.1038/sj.jid.5700639. Epub 2006 Nov 23.
Piebald trait leukoderma results from "loss-of-function" mutations in the kit gene. Correlations between mutation type and clinical phenotype have been reported. However, mutation classification has been mainly based on the clinical features of patients. The aim of this study was to get a better understanding of the pathogenesis of human piebaldism by establishing whether the kit mutation type may affect the in vitro survival/proliferation of patient melanocytes. Overall, the research was finalized to implement the clinical application of the autologous cultured epidermis in the treatment of piebald patients. Seven patients, who were transplanted with autologous in vitro reconstituted epidermis, showed an average percentage of repigmentation of 90.7. Six novel and one previously reported mutations were found and their postulated effects discussed in relation to the clinical phenotype and in vitro behavior of epidermal cells. Although mutation type did not impair repigmentation given by autotransplantation, it was shown to influence the survival/proliferation of co-cultured melanocytes and keratinocytes. In particular, tyrosine kinase domain mutations were found with melanocyte loss and keratinocyte senescence during expansion of epidermal cultures. Results indicate that the clinical application of cultured epidermis in piebald patients may be optimized by investigating mutation functional effects before planning surgical operations.
斑驳病性白斑是由kit基因的“功能丧失”突变引起的。已有报道突变类型与临床表型之间的相关性。然而，突变分类主要基于患者的临床特征。本研究的目的是通过确定kit突变类型是否可能影响患者黑素细胞的体外存活/增殖，从而更好地理解人类斑驳病的发病机制。总体而言，该研究最终实现了自体培养表皮在斑驳病患者治疗中的临床应用。7例接受自体体外重建表皮移植的患者，色素再沉着的平均百分比为90.7。发现了6种新的突变和1种先前报道的突变，并就其假定的影响与表皮细胞的临床表型和体外行为进行了讨论。虽然突变类型并不影响自体移植后的色素再沉着，但已表明它会影响共培养的黑素细胞和角质形成细胞的存活/增殖。特别是，在表皮培养物扩增过程中发现酪氨酸激酶结构域突变伴有黑素细胞丢失和角质形成细胞衰老。结果表明，在计划手术前通过研究突变的功能效应，可能会优化培养表皮在斑驳病患者中的临床应用。
