Sex-Specific Angiogenic Responses of Vascular Cells to Simulated Microgravity

血管细胞对模拟微重力的性别特异性血管生成反应

• 批准号: 10606937
• 负责人: Christopher M. Ludtka
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-16 至 2025-08-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10606937
• 关键词: 3-Dimensional; Address; Adhesions; Angiogenic Factor; Behavior; Biological; Biomimetics; Bioreactors; Blood; Blood Vessels; Cell Culture Techniques; Cells; Cellular Structures; Clinical assessments; Coculture Techniques; Confocal Microscopy; Culture Techniques; Data; Development; Devices; Drug Implants; Endothelial Cells; Environment; Evaluation; Experimental Designs; Force of Gravity; Foundations; Future; Genetic; Genomics; Germ Cells; Goals; Histologic; Hormonal; Human; Image Analysis; Immunohistochemistry; Implant; In Vitro; Incidence; Inflammation; Inflammatory; Investigation; Knowledge; Literature; Macrophage; Measures; Methodology; Methods; Microgravity Simulation; Mission; Modeling; Molecular Chaperones; Nature; Organism; Pathologic; Pathology; Pharmacy (field); Postmenopause; Premenopause; Production; Reporting; Research; Research Project Grants; Review Literature; Rotation; Self Assessment; Sex Differences; Signal Transduction; Structure; Testing; Tissue Engineering; Umbilical vein; United States National Institutes of Health; Vascularization; Woman; Work; angiogenesis; cell type; clinical application; clinical care; clinical translation; experimental study; implantation; improved; insight; men; monocyte; mortality; multiplex assay; nano-string; novel strategies; response; scaffold; self organization; sex; success; transcriptome; transcriptomics

Project Summary / Abstract Vascularization has long been a hurdle in the development of tissue engineering, either for therapeutic implants or biomimetic models. A number of cell, signal, scaffold, and culture techniques and methods have been investigated for the creation of vascular structures and ultimately networks. In this context, endothelial cells are a critical cell type, as they comprised the intimal layer of vessels. Is has also been reported that macrophages, in co-culture with endothelial cells, can provide pro-vascularization effects as signalers and chaperones. Another strategy for the creation of vascular structures of endothelial cells has been culture in simulated microgravity, where endothelial cells self-organize into tubules and spheroids, which is not seen under equivalent normal gravity conditions. Lastly, in the evaluation of endothelial cell responses, vascularization, and even vascular pathology, sex-differences have been demonstrated, though sex as a biological variable is often not reported or considered historically in the existing literature. As such, this project aims to (1) investigate the hormonal and genomic sex-dependent effects of simulated microgravity on endothelial cells regarding key factors of vascularization, and (2) investigate endothelial cell – macrophage co-culture in simulated microgravity for effects on keys factors of vascularization, while also considering sex as a biological variable. The experimental design of this study will evaluate critical aspects of genetic expression and the tubule and spheroid structures formed from the proposed culture methodology. The data will be evaluated in the context of sex-differences in these vascular cells. The significance of this work is the development of the unique culture environment represented by simulated microgravity that has shown promising results in the creation of vascular structures. Further significance is the insight into sex-differences of vascular cells in the context of tissue engineering and vascularization. Specifically, the development of novel strategies for producing vascular constructs could improve existing methods for the creation of implants and biomimetic models, as well as our understanding of sex-differences for the purposes of more personalized translational and clinical assessment and care.

项目总结/摘要 血管化长期以来一直是组织工程发展的一个障碍，无论是用于治疗性植入物， 或仿生模型。许多细胞、信号、支架和培养技术和方法已经被公开， 研究血管结构和最终网络的创建。在这种情况下，内皮细胞是 这是一种关键的细胞类型，因为它们构成了血管的内膜层。据报道，巨噬细胞， 在与内皮细胞共培养时，可以作为信号分子和分子伴侣提供促血管形成作用。另一 用于创建内皮细胞的血管结构的策略已经在模拟微重力下培养， 其中内皮细胞自组织成小管和球状体，这在同等的正常情况下是看不到的。 重力条件。最后，在评价内皮细胞反应、血管化甚至血管反应时， 在病理学上，性别差异已经得到证实，尽管性别作为一个生物学变量往往没有报告， 在现有文献中被历史地考虑。因此，本项目旨在（1）研究激素和 模拟微重力对内皮细胞的基因组性别依赖性影响， 血管化，和（2）研究内皮细胞-巨噬细胞在模拟微重力下共培养的影响 血管化的关键因素，同时也考虑到性别作为一个生物变量。实验设计 本研究的第一部分将评估基因表达和形成的小管和球体结构的关键方面， 文化的方法论。这些数据将在性别差异的背景下进行评估， 血管细胞。这部作品的意义在于它所代表的独特文化环境的发展 通过模拟微重力，在血管结构的创建方面显示出有希望的结果。进一步 重要的是在组织工程的背景下深入了解血管细胞的性别差异， 血管化特别是，开发新的生产血管结构的策略， 改进现有的植入物和仿生模型的创建方法，以及我们对 性别差异，以便进行更加个性化的翻译和临床评估和护理。