Sex-Specific Angiogenic Responses of Vascular Cells to Simulated Microgravity

项目摘要/摘要 血管化长期以来一直是组织工程学发展的障碍，无论是对于治疗性植入物 或者仿生模型。许多细胞、信号、支架和培养技术和方法已经被 研究了血管结构和最终网络的建立。在这种情况下，内皮细胞是 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， 在与内皮细胞的共培养中，可以作为信号转导和伴侣提供促血管形成的作用。另一个 已经在模拟微重力中培养了创建内皮细胞血管结构的策略， 血管内皮细胞自组织成小管和球体，这在等值正常情况下是看不到的 重力条件。最后，在评估内皮细胞反应时，血管化，甚至血管 病理上，性别差异已经被证明，尽管性别作为一个生物变量通常没有报道或 在现有文献中被认为是历史上的。因此，这个项目的目的是(1)研究荷尔蒙和 模拟微重力对血管内皮细胞的性别依赖性影响 血管形成，以及(2)研究模拟微重力下内皮细胞-巨噬细胞共培养的影响 关于血管形成的关键因素，同时也将性别视为生物学变量。实验设计 这项研究将评估基因表达的关键方面以及形成的管状和椭圆形结构 来自提议的文化方法论。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所表现的独特文化环境的发展 通过模拟微重力，在创建血管结构方面显示了有希望的结果。进一步 意义在于在组织工程和组织工程的背景下洞察血管细胞的性别差异 血管形成。具体地说，生产血管构造的新策略的开发可能 改进现有的创建植入物和仿生模型的方法，以及我们对 性别差异，用于更个人化的转译和临床评估和护理。

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.