Sex-Specific Angiogenic Responses of Vascular Cells to Simulated Microgravity

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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.