HUMAN SKIN CULTURES--IN VIVO AND IN VITRO

该补助金的最终目的是确定和修改监管 人胎儿角朊细胞向器官定向分化前的影响因素 发育和终末分化。 人类胎儿的皮肤 移植到裸鼠，在那里正常的人类发育序列可以 进行评估和修改。 此外，体外胎儿角质形成细胞培养 系统将被开发，以确定机制和改性剂， 角质形成细胞生长和分化可能在胎儿和 成体角质形成细胞 通过使用这两个系统，器官发育和 将研究人胎儿皮肤的终末分化。 通过 在两个系统中化学操纵人胎儿表皮发育， 胎儿角质形成细胞的生物学和生化反应 将研究发展。 一旦胎儿正常发育 详细介绍了这两个系统，主要扰动将通过 表皮和真皮组织的重组移植物， 角质形成细胞和成纤维细胞。 这些移植物将通过 先前鉴定的化学介质包括13-顺式-视黄酸。 发展的归纳影响将被详细地确定。 然后，将诱导影响应用于表皮疾病 增殖（鱼鳞病、外胚层发育不良、银屑病、表皮痣） 和真皮-表皮连接处的疾病（大疱性表皮病）。 使用成熟组织、胎儿组织和患病组织的组合， 将评估疾病引起的变化。 人类胎儿的修饰 通过病变组织的发育， 控制疾病。

The ultimate aim of this grant is to identify and modify the regulatory factors of the human fetal keratinocyte prior to commitment toward organ development and terminal differentiation. Human fetal skin will be transplanted to nude mice where the normal human developmental sequence can be evaluated and modified. In addition in-vitro fetal keratinocyte culture systems will be developed to identify mechanisms and modifiers of keratinocyte growth and differentiation which may differ between fetal and adult keratinocytes. By using these two systems, organ development and terminal differentiation of human fetal skin will be studied. By chemically manipulating human fetal epidermal development in both systems, the biological and biochemical responses of fetal keratinocytes during development will be studied. Once the normal process of fetal development is detailed in both systems, major perturbations will be introduced through recombinant grafts of epidermal and dermal tissues and eventually keratinocytes and fibroblasts. These grafts will be modulated by previously identified chemical mediators including 13-cis-retinoic acid. The inductive influences of development will be identified in detail. The inductive influences then will be applied to diseases of epidermal proliferation (ichthyosis, ectodermal dysplasia, psoriasis, epidermal nevi) and diseases of the dermal-epidermal junction (epidermolysis bullosa). Using combinations of mature, fetal and diseased tissues, analysis of disease-induced variations will be evaluated. Modifications of human fetal development by diseased tissues will identify abnormalities of cellular control in disease.