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HUMAN SKIN CULTURES--IN VIVO AND IN VITRO

人类皮肤培养——体内和体外

基本信息

批准号：
3319577
负责人：
ALFRED T LANE
金额：
$ 11.86万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-01-01 至 1988-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3319577
关键词：
athymic mouse cell differentiation congenital ichthyosis epidermolysis bullosa fibroblasts human fetus tissue keratinocyte psoriasis retinoate skin transplantation tissue /cell culture

项目摘要

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.

这项授权的最终目的是确定和修改监管人胎儿角质形成细胞向器官着床前的因素发育和末端分化。人类胎儿皮肤将会是移植到裸鼠身上，在那里正常的人类发育序列可以被评估和修改。此外，胎儿角质形成细胞的体外培养将开发系统来识别机制和修饰物角质形成细胞的生长和分化可能与胎儿和成人角质形成细胞。通过使用这两个系统，器官开发和将研究人胎儿皮肤的终末分化。通过在这两个系统中对人类胎儿表皮的发育进行化学操作，胎儿角质形成细胞在胚胎发育过程中的生物学和生化反应将对发展进行研究。一旦胎儿发育的正常过程在这两个系统中都有详细介绍，主要的扰动将通过重组的表皮和真皮组织移植物，最终角质形成细胞和成纤维细胞。这些移植物将由此前发现的化学介体包括13-顺式维甲酸。将详细确定发展的诱致性影响。然后，感应影响将应用于表皮疾病。增殖(鱼鳞病、外胚层发育不良、牛皮癣、表皮痣) 以及真皮-表皮交界处的疾病(大疱性表皮松解症)。利用成熟、胎儿和疾病组织的组合，分析将对疾病引起的变异进行评估。对人胎儿的修饰病变组织的发育将识别细胞的异常对疾病的控制。