NSF Award
2433264
The placenta is a critical temporary organ that develops during pregnancy impacting lifelong health of both mother and infant. Many pregnancy-related complications are the result of a placental abnormality, including preeclampsia. Preeclampsia is a condition often clinically diagnosed by the onset of high blood pressure after the 20th week of pregnancy, which can necessitate preterm delivery. Preeclampsia occurs in 1 out of 12 pregnancies resulting in 76,000 maternal deaths and 500,000 infant deaths each year worldwide. Understanding and treating preeclampsia is challenging because the placenta is also one of the least understood human organs. The proposed work focuses on developing new 3D models using placental cells acquired after delivery from patients with preeclampsia. In addition, the proposed work includes research opportunities for undergraduate and high school students to engage in the project. The PI’s lab will also lead biomaterials outreach activities, particularly showing how biomaterials are advancing women’s health, with middle and high school students through local services that provide after and out-of-school activities.<br/><br/>Preeclampsia is a disease state of the placenta, an organ that is not well understood, necessitating new model systems to study it. Trophoblast cells are the main cell type composing the placenta, with important roles including nutrient and waste transport as well as invading the decidualized endometrium. There are few in vitro cell models available for preeclampsia, and currently there are no 3D in vitro systems using patient-derived preeclamptic trophoblast cells. The goal of the this project is to develop a preeclamptic trophoblast 3D spheroid model that enables studies of trophoblast invasiveness, a critical process for overall placental health. In Objective 1, preeclamptic trophoblast spheroid models will be developed and characterized. The spheroids will be incorporated within extracellular matrices mimicking the maternal endometrium. In Objective 2, the preeclamptic spheroid models will be used to investigate trophoblast cell invasion at the placental-endometrial interface. Comparisons will be made between spheroids developed using trophoblasts from either healthy patients or patients with diagnosed preeclampsia. The engineering advances of the proposed work include (1) Designing the appropriate culture conditions to develop spheroids that can be readily maintained and are repeatable, (2) Engineering the interface between the placenta and maternal endometrium by incorporating the spheroids within a methacrylated gelatin (GelMa) matrix, and (3) Developing the matrix composition and stiffness representative of the endometrium during pregnancy while also maintaining preeclamptic spheroid viability over time.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
