The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression
The Three-Dimensional Human Skin Reconstruct Model: a Tool to Study Normal Skin and Melanoma Progression
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DOI：
10.3791/2937
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发表时间：
2011-08-01
影响因子：
1.2
通讯作者：
Herlyn, Meenhard
中科院分区：
文献类型：
--
作者：
Li, Ling;Fukunaga-Kalabis, Mizuho;Herlyn, Meenhard
大多数实验性皮肤生物学的体外研究都是在二维（2D）单培养中进行的，而越来越多的证据表明，当细胞在三维细胞外基质中生长并与其他细胞相互作用时，细胞的行为会有所不同（1-5）。小鼠模型已被广泛用于体内组织形态发生的研究。然而，小鼠和人类皮肤在细胞结构和生理上存在显著差异，这使得小鼠研究很难推断到人类。由于小鼠皮肤中的黑色素细胞大多位于毛囊中，因此它们与主要位于表皮基底层的人类皮肤细胞具有不同的生物学特性。最近3D人体皮肤重建模型的发展使该领域能够研究不同细胞类型之间的细胞-基质和细胞-细胞相互作用。重建的结构包括：由成纤维细胞嵌入胶原I基质的“真皮层”、由分层、分化的角质形成细胞组成的“表皮”和将表皮与真皮层分开的功能性基底膜。胶原蛋白提供支架、营养传递和细胞间相互作用的潜力。包含黑素细胞的3D皮肤模型概括了人类皮肤中黑素细胞稳态和黑色素瘤进展的自然特征。在体内，重建皮肤中的黑色素细胞定位于基底膜，其间散布着基底层角质形成细胞。黑色素瘤细胞在体内表现出反映原始肿瘤分期的相同特征（RGP、VGP和转移性黑色素瘤细胞）。最近，在人类真皮中发现了真皮干细胞(6)。这些多能干细胞可以迁移到表皮并分化为黑色素细胞。
Most in vitro studies in experimental skin biology have been done in 2-dimensional (2D) monocultures, while accumulating evidence suggests that cells behave differently when they are grown within a 3D extra-cellular matrix and also interact with other cells (1-5). Mouse models have been broadly utilized to study tissue morphogenesis in vivo. However mouse and human skin have significant differences in cellular architecture and physiology, which makes it difficult to extrapolate mouse studies to humans. Since melanocytes in mouse skin are mostly localized in hair follicles, they have distinct biological properties from those of humans, which locate primarily at the basal layer of the epidermis. The recent development of 3D human skin reconstruct models has enabled the field to investigate cell-matrix and cell-cell interactions between different cell types. The reconstructs consist of a "dermis" with fibroblasts embedded in a collagen I matrix, an "epidermis", which is comprised of stratified, differentiated keratinocytes and a functional basement membrane, which separates epidermis from dermis. Collagen provides scaffolding, nutrient delivery, and potential for cell-to-cell interaction. The 3D skin models incorporating melanocytic cells recapitulate natural features of melanocyte homeostasis and melanoma progression in human skin. As in vivo, melanocytes in reconstructed skin are localized at the basement membrane interspersed with basal layer keratinocytes. Melanoma cells exhibit the same characteristics reflecting the original tumor stage (RGP, VGP and metastatic melanoma cells) in vivo. Recently, dermal stem cells have been identified in the human dermis (6). These multi-potent stem cells can migrate to the epidermis and differentiate to melanocytes.