Microarray Facility Project

微阵列设施项目

基本信息

批准号：
6314770
负责人：
R B Rutherford
金额：
$ 24.22万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-15 至 2003-07-31
项目状态：
已结题

项目摘要

Substantial personal and financial costs are associated with congenital and acquired loss of oral tissue structure and function, yet few effective therapeutic strategies for the repair or regeneration of oral tissues are available. Autologous tissue transplantation is severely limited by the availability of sufficient donor tissue and donor site morbidity. The effectiveness of allogenic transplant materials is limited. Tissue engineering combines principles of chemistry, biology and engineering to effect solutions to these problems. Strategies include direct local delivery of tissue inducing signaling molecules, genes for a variety of key proteins and cell/carrier constructs. However therapy based upon delivery of tissue inductive signaling molecules such as the bone morphogenetic proteins or genes (gene therapy) is still in development and the clinical indications for these approaches will be limited. Therefore methods to produce substitute tissue transplants are being developed and we have begun to apply these strategies and methods to the restoration of oral tissue structure and function. Our immediate goal is to develop cell-based tissue engineering for the repair or regeneration of specific oral tissues; dental pulp, dentin and bone. The ultimate clinical utility of a cell based approach to tissue engineering depends in part upon the availability and accessibility of cell capable of appropriate differentiation and morphogenesis. Therefore this project asks the question; do cells need to be derived from the tissue targeted for repair or can cells derived from easily biopsied tissues be utilized? Little is known about the capacity of cells cultured from oral tissues such as pulp and gingiva to effect tissue repair in vivo, however recent data reveal that the potential of cells varies with tissue source. Our general hypothesis is that there are optimum cell/carrier constructs (neotissues) for the development of specific, mature adult tissues in vivo. To test this hypothesis in the context of developing neotissues for the regeneration of dental pulp, dentin, and bone, our specific aims are: 1) optimize basal in vitro development parameters and characterize the tissue formed in vivo by human, gingival, dental pulp and marrow stromal neotissues using two prototype scaffolds, 2) study the expression of osteoblast and odontoblast differentiation genes, and 3) study the effects of signaling molecules associated with bone and dentin regeneration in vivo on oral neotissue development in vitro and in vivo. Data from these experiments is expected to lead to the design of clinical trials testing the safety and efficacy or oral neotissues as well as provide essential data for the use of neotissues as in vitro and in vivo models of reparative tissue formation.

大量的个人和财务成本与先天性相关口腔组织结构和功能的获得性丧失，但很少口腔修复或再生的有效治疗策略纸巾是可用的。自体组织移植严重受到足够供体组织和供体部位可用性的限制发病率。同种异体移植材料的有效性是有限的。组织工程结合了化学、生物学原理和工程来实现这些问题的解决方案。策略包括直接局部递送组织诱导信号分子，各种关键蛋白质和细胞/载体构建体的基因。然而，基于组织诱导信号传导的治疗分子，例如骨形态发生蛋白或基因（基因疗法）仍在开发中，这些药物的临床适应症方法将受到限制。因此，生产替代品的方法组织移植正在开发中，我们已经开始应用这些口腔组织结构修复的策略和方法功能。我们的近期目标是开发基于细胞的组织工程用于特定口腔组织的修复或再生；牙髓，牙本质和骨头。基于细胞的方法的最终临床效用组织工程部分取决于可用性和能够适当分化的细胞的可及性和形态发生。因此这个项目提出了这样的问题：细胞需要吗源自修复目标组织或源自细胞可以利用容易活检的组织吗？人们对此知之甚少从牙髓和牙龈等口腔组织培养的细胞的能力影响体内组织修复，然而最近的数据表明细胞的潜力随组织来源的不同而变化。我们的一般假设是有最佳的细胞/载体结构（新生组织）体内特定的、成熟的成体组织的发育。为了测试这个在发育新组织再生的背景下的假设牙髓、牙本质和骨骼，我们的具体目标是： 1) 优化基础体外发育参数并表征形成的组织人体内、牙龈、牙髓和骨髓基质新组织使用两个原型支架，2）研究成骨细胞的表达和成牙本质细胞分化基因，3) 研究信号传导的影响口腔体内与骨和牙本质再生相关的分子体外和体内新组织发育。这些实验的数据预计将导致测试安全性的临床试验设计和功效或口腔新组织，并提供必要的数据使用新组织作为修复的体外和体内模型组织形成。