INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP

个人博士前牙科科学家奖学金

• 批准号: 6397736
• 负责人: DARNELL KAIGLER
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6397736
• 关键词: BCL2 gene /protein; Retroviridae; SCID mouse; angiogenesis; angiogenesis factor; biodegradable product; bone morphogenetic proteins; capillary; enzyme linked immunosorbent assay; immunocytochemistry; method development; northern blottings; osteoblasts; osteogenesis; polymers; tissue engineering; tissue support frame; transfection /expression vector; vascular endothelium; western blottings

The field of tissue engineering has developed due to the inadequate supply of organs and tissues for patients requiring organ/tissue replacement. An attractive alternative to organ and tissue transplantation that could immensely expand clinicians' ability to treat patients requiring new organs and tissues is the selective transplantation of the appropriate cell type(s). Transplanting cell populations on biodegradable polymer matrices in order to engineer a functional tissue mass from these transplanted cells is an intriguing strategy. However, the survival of these cells is dependent on diffusion of nutrients and waste products between the transplanted cells on the matrix and the vasculature existing in the surrounding host tissue. Currently, this vascular network is the limiting factor in allowing the engineering of large-scale masses of tissue capable of forming whole organs. The proposed research focuses on strategies to increase the vascular network within these polymer matrices in order to create significant amounts of bone tissue capable of replacing osseous defects. The specific aims of this proposal are: Aim 1-To define strategies to engineer microvascular endothelial cells to produce growth factors/mediators that a) will induce a vigorous and sustained angiogenic response, and b) will induce bone development and growth from osteogenic precursors. We will initially look at the mediators Bcl-2, angiopoietin (two potent inducers of angiogenesis), and the osteogenic mediator BMP-2; Aim 2- To incorporate these different endothelial cell populations into biodegradable polymer matrices and to test their individual and combined abilities to form capillaries in vitro and in vivo; Aim 3- To determine the baseline bone formation when osteo-progenitor cells are transplanted on a biodegradable matrix; Aim 4-To determine if an appropriate combination of endothelial cells, osteo-progenitor cells, and matrix, as determined in Specific Aims 1-3, will result in a sustained and vigorous angiogenic response in vivo (SCID mouse model) capable of supporting bone development from osteo-progenitor cells.

由于需要器官/组织替换的患者的器官和组织供应不足，组织工程领域得到了发展。 器官和组织移植的一个有吸引力的替代方案是选择性移植适当的细胞类型，它可以极大地提高临床医生治疗需要新器官和组织的患者的能力。将细胞群移植到可生物降解的聚合物基质上，以便从这些移植的细胞中改造出功能性组织块是一种有趣的策略。 然而，这些细胞的存活取决于基质上的移植细胞与周围宿主组织中存在的脉管系统之间营养物质和废物的扩散。目前，这种血管网络是对能够形成整个器官的大规模组织进行工程改造的限制因素。 拟议的研究重点是增加这些聚合物基质内的血管网络的策略，以产生大量能够替代骨缺损的骨组织。 该提案的具体目标是： 目标 1 - 定义改造微血管内皮细胞以产生生长因子/介质的策略，a）将诱导强烈且持续的血管生成反应，b）将诱导骨发育和成骨前体的生长。 我们首先将研究介质 Bcl-2、血管生成素（两种有效的血管生成诱导剂）和成骨介质 BMP-2；目标 2- 将这些不同的内皮细胞群整合到可生物降解的聚合物基质中，并测试它们在体外和体内形成毛细血管的单独和组合的能力；目标 3-确定将骨祖细胞移植到可生物降解基质上时的基线骨形成；目标 4-确定内皮细胞、骨祖细胞和基质的适当组合（如具体目标 1-3 中确定的那样）是否会导致体内持续且强烈的血管生成反应（SCID 小鼠模型），从而能够支持骨骼由骨祖细胞发育而来。