Stem Cell-Based Modeling of Trophoblast Development in Normal Pregnancies and in Pre-eclampsia

Abstract Authors: Laura C. Schulz
Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO USA

Abstract Text:

Defects in human placental development are associated with infertility, pregnancy loss, placenta previa and accreta, preeclampsia, and intrauterine growth restriction amongst other conditions. While placental tissue is readily available at delivery, many of these conditions are thought to arise early in pregnancy, often long before symptoms arise. Additionally, any delivered placenta represents only a single snapshot in time. These limitations present challenges for researchers trying to understand the progression of placental development under normal or pathological conditions. Induced stem cell technologies provide a potential solution to this challenge. Tissues collected at delivery may be reprogrammed into stem cells that represent earlier stages of development, and differentiation can be followed over time. Taking such an approach, we have identified factors expressed in the placenta only in first trimester, and found that cells derived from preeclamptic pregnancies maintain some differences from control cells, even after reprogramming and differentiation. Recent results suggest that stem cells in a single culture are heterogeneous in their trophoblast differentiation potential, and have identified multiple subpopulations.  Advances in three-dimensional culture facilitate spatial relationships amongst stem cell derived populations that more closely resemble the placenta in vivo. Nonethless, challenges remain in determining how cell states and cell identities in trophoblast stem cell cultures relate to those in vivo.