Lauren Hesse
Research Mentor(s): Russell Urie
Research Mentor School/College/Department: Biomedical Engineering
Presentation Date: 08/03/2022
Presentation Type: Poster
Poster Number: 42
Session: Session II: 1:30 – 2:20pm
Room: League Ballroom
Authors: Lauren Hesse, Russell Urie, Elizabeth Lombard, Chengchuan Xiao, and Lonnie Shea
Abstract
Background: No technology currently exists that can predict prenatal complications due to immune rejection. The prevalence of pregnancy complications such as gestational diabetes and preeclampsia have increased by >15% between 2014 and 2018 and this trend has not reversed. Women with pregnancy complications are twice as likely to have childbirth complications such as eclampsia, cardiomyopathy, embolism, sepsis, and respiratory distress. Additionally, 26% of all pregnancies end prior to 20 weeks due to spontaneous abortion (miscarriage). For roughly half of all pregnancy complications, there is an unknown immunological basis. Because of this, a minimally invasive assay to monitor the state of pregnancy and predict prenatal complications could transform the field of obstetrics.
Proposal: The Shea lab has developed microporous biomaterial scaffolds as synthetic immunological niches which facilitate investigating disease dynamics and immune responses without disrupting native tissue. In this work, we will employ minimally-invasive scaffolds to capture the longitudinal immune domain of healthy and miscarriage-prone rodent pregnancies.
Data/Results: Through analysis of flow cytometry results, we found that there was a sharp rise in CD4+, CD8+, and anergic T cells in the uterus during syngeneic pregnancy, but not regulatory T cells (Tregs) Additionally, a greater T cell population across all subsets (helper, cytotoxic, Tregs, and anergic) was present in the placentae during allogeneic pregnancy. These findings are consistent with the hypothesis that additional immunosuppression, mediated by Tregs, is required during allogeneic pregnancy than its syngeneic counterpart. Most interestingly, there is a significant difference in proliferation between activated T cells cultured with allogeneic and syngeneic scaffold-derived cells, which mirrors the difference displayed by activated T cells cultured with allogeneic and syngeneic primary cells from the uterine microenvironment (uterus and placenta). Allogeneic and syngeneic primary cells isolated from the blood and spleen did not have a significantly different effect on T cell proliferation. This suggests that the cells captured by the scaffold better recapitulate the immune activity of the uterine microenvironment than those extravasated cells found in the spleen or blood.
Conclusions: Our main conclusions are two-fold. One, scaffolds accumulate both innate and adaptive immune cells. Two, cells in the scaffold recapitulate the behavior of cells in the uterine microenvironment, that is, they have an immunosuppressive effect when cells in the womb demonstrate immunosuppression, which is not faithfully mirrored in the spleen/peripheral blood.
Future Directions: Long term, we will characterize the dynamics of immune cell types in the placenta and the tissue engineered synthetic placental niche to generate a predictive gene expression signature of healthy and miscarriage-prone pregnancies. We also intend to utilize porogen leaching to manufacture microporous polymeric scaffolds made from poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or silk coated PCL (silk-PCL). These scaffolds will act as a minimally invasive prenatal monitoring tool to collect a significant number of fetal and immune cells that are more phenotypically similar to those present in the uterine microenvironment than peripheral blood.
