THE EFFECTS OF AGES ON CELL BEHAVIOR WITHIN A 3D VASCULAR TISSUE CONSTRUCT

年龄对 3D 血管组织结构内细胞行为的影响

• 批准号: 8167974
• 负责人: Heather Fahlenkamp
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167974
• 关键词: Advanced Glycosylation End Products; Area; Arterial Fatty Streak; Atherosclerosis; Award; Basement membrane; Blood Vessels; Bovine Serum Albumin; Cell physiology; Collaborations; Collagen Type IV; Complications of Diabetes Mellitus; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Endothelial Cells; Funding; Future; Genus Capra; Glucose; Goals; Grant; Human; Hyperglycemia; Immune; In Vitro; Individual; Inflammatory; Institution; Lead; Link; Mentors; Modeling; Modification; Notification; Physiological; Pilot Projects; Research; Research Personnel; Research Project Grants; Resources; Source; Supporting Cell; System; Techniques; Therapeutic; Tissue Model; Tissues; United States National Institutes of Health; Work; age effect; cell behavior; cell motility; meetings

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Effect of AGEs on Cell Behavior Within a 3D Vascular Tissue Construct This start of this project was delayed and the work has been limited due to the delay of formal funding from NIH for the Pilot Project. Since notification of the Pilot Project award in early October, I have attended an advisory board meeting, as well as monthly PJI meetings at OUHSC. For the EAC/IAC meeting in early November, I presented my research highlights for past work with the 3D vascular tissue model that led to the development of my pilot project. I received some useful information from the committee that has been used to further develop my current research project. For the monthly PJI meetings, each PJI is taking a turn to present current research findings to the group, which is followed by a group discussion. Dr. Don Capra has also been attending the monthly PJI meetings to serve as a research mentor. The individual presentations and the group discussion allows me to understand the research areas of other PJIs that leads to more interaction and possible future collaborations. Progress on the pilot project includes modifications to the 3D vascular tissue model so that it mimics physiological conditions associated with the vascular regions prone to atherosclerosis. This includes using human aortic endothelial cells and using type IV collagen to create a basement membrane to support the cells. Due to these changes, the system is being characterized and compared to the previous model. This includes functional analyses of the endothelial cells under both normal and inflammatory conditions associated with atherosclerosis. Additional work on the project includes the formation and characterization of advanced glycosylation end products (AGE). A proposed mechanism linking hyperglycemia to diabetic complications like atherosclerosis is the increase of advanced glycosylation end products formation. A standard technique using bovine serum albumin and glucose was used for in vitro AGE formation. The modified 3D vascular tissue model will be used to study the effect of AGE on endothelial cell function and immune cell migration and differentiation that would lead to atherosclerotic plaque formation. The goal of this project is to is to use the 3D vascular tissue construct to determine the underlying mechanisms associated with hyperglycemia and atherosclerosis in order to develop new preventative and/or therapeutic strategies.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 AGE 对 3D 血管组织结构内细胞行为的影响 由于 NIH 为试点项目提供正式资金的延迟，该项目的启动被推迟，工作也受到限制。 自从 10 月初收到试点项目授予通知以来，我参加了顾问委员会会议以及 OUHSC 每月举行的 PJI 会议。 在 11 月初的 EAC/IAC 会议上，我介绍了我过去在 3D 血管组织模型方面的工作的研究重点，这些工作促成了我的试点项目的开发。 我从委员会收到了一些有用的信息，这些信息已用于进一步开发我当前的研究项目。 在每月一次的 PJI 会议上，每个 PJI 轮流向小组介绍当前的研究成果，然后进行小组讨论。 Don Capra 博士还参加了每月一次的 PJI 会议，担任研究导师。 个人演讲和小组讨论让我了解其他 PJI 的研究领域，从而带来更多的互动和未来可能的合作。 该试点项目的进展包括对 3D 血管组织模型的修改，使其能够模拟与容易发生动脉粥样硬化的血管区域相关的生理条件。 这包括使用人类主动脉内皮细胞和使用 IV 型胶原蛋白来创建基底膜来支撑细胞。 由于这些变化，我们正在对系统进行表征并与之前的模型进行比较。 这包括在正常和与动脉粥样硬化相关的炎症条件下内皮细胞的功能分析。 该项目的其他工作包括高级糖基化终产物 (AGE) 的形成和表征。 一种将高血糖与动脉粥样硬化等糖尿病并发症联系起来的机制是高级糖基化终产物形成的增加。使用牛血清白蛋白和葡萄糖的标准技术用于体外 AGE 形成。 修改后的 3D 血管组织模型将用于研究 AGE 对内皮细胞功能以及免疫细胞迁移和分化的影响，从而导致动脉粥样硬化斑块形成。 该项目的目标是使用 3D 血管组织构建体来确定与高血糖和动脉粥样硬化相关的潜在机制，以便开发新的预防和/或治疗策略。