Meyer L J, Schmidt L A, Goldgar D E, Piepkorn M W
Department of Medicine (Dermatology), University of Utah School of Medicine, Salt Lake City, USA.
Am J Dermatopathol. 1995 Aug;17(4):368-73. doi: 10.1097/00000372-199508000-00011.
Melanocytic nevi (n = 406) covering a range of sizes and gross morphologic features were excised from human donors, sampled for histologic diagnosis, and transplanted to athymic (nude) mice. Ninety percent of these xenografts survived transplantation, of which a subset was irradiated daily with ultraviolet light to promote neoplastic transformation. Over 16 weeks of observation, nearly all grafts histologically showed focal inflammatory cell infiltration and fibrosis, progressing in approximately 30% of grafts to complete regression at final observation. During the inflammatory phase, the nevi often had junctional intraepidermal melanocytic hyperplasia in a lentiginous pattern, with cytologic hypertrophy, dendritic morphology, and hypermelaninization. These changes were evident in approximately 20-30% of nevi where they were absent before transplantation, suggesting that host factors, such as those related to the immune response, had stimulated growth. Graft survival was independent of nevus size and initial histologic diagnosis. No melanomas developed in any of the grafts, either spontaneously or with ultraviolet irradiation. These results indicate that successful transplantation can be achieved in a high proportion of human nevus xenografts and that the majority survive for a period of time that would be sufficient for experimental studies. The host response, however, has effects on intraepidermal melanocytic growth that lead to progressive fibrous replacement of the nevus, introducing significant artifacts that compromise the model. Furthermore, malignant transformation of engrafted melanocytes seems to be a rare event, which would limit studies of neoplastic progression in the transplanted melanocytes. Nonetheless, the intraepidermal melanocytic pattern described here evidently constitutes one pattern of melanocyte growth that could be exploited experimentally for studies of growth and differentiation control in melanocytes.
从人类供体切除了406个黑素细胞痣，这些痣大小不一，具有多种大体形态特征，取样用于组织学诊断后移植到无胸腺（裸）小鼠体内。这些异种移植中有90%在移植后存活，其中一部分每天接受紫外线照射以促进肿瘤转化。在16周的观察期内，几乎所有移植组织在组织学上都显示有局灶性炎性细胞浸润和纤维化，在最终观察时约30%的移植组织进展为完全消退。在炎症期，痣通常在表皮内呈雀斑样交界性黑素细胞增生，伴有细胞肥大、树突状形态和色素沉着过度。这些变化在移植前不存在的约20%-30%的痣中很明显，表明宿主因素，如与免疫反应相关的因素，刺激了生长。移植存活与痣的大小和初始组织学诊断无关。任何移植组织中均未自发或经紫外线照射发生黑色素瘤。这些结果表明，高比例的人类痣异种移植能够成功实现，且大多数能存活一段时间，足以进行实验研究。然而，宿主反应对表皮内黑素细胞生长有影响，导致痣逐渐被纤维组织替代，引入了显著的假象，损害了该模型。此外，移植的黑素细胞发生恶性转化似乎是罕见事件，这将限制对移植黑素细胞肿瘤进展的研究。尽管如此，这里描述的表皮内黑素细胞模式显然构成了黑素细胞生长的一种模式，可用于黑素细胞生长和分化控制的实验研究。
