Modeling preeclampsia: An emerging role for stem cells

Preeclampsia is specific to human pregnancy and is cured by delivery of the gestation. The disease is particularly difficult to study because its underpinnings likely occur very early in pregnancy, but its detection is delayed until the second or third trimester. In vivo study of disease pathogenesis is limited by ethical prohibitions and logistical limitations to our access to the earliest events in human gestation, some of which occur before the first missed menses and clinical detection of the pregnancy. Because the disease does not appear to spontaneously occur in any readily available animal model, study of the disorder in animals is limited by models that mimic some, but not all, of the disease manifestations. The disease may be largely the result of abnormalities in placentation, so human trophoblast cells have been used to allow in vitro study of the disorder. Unfortunately, primary cell lines are typically short-lived while immortalized, or cancer-derived cell lines may carry genetic or epigenetic changes that alter cellular function or morphologic features in ways that may confound result interpretation. Recent advances in stem cell technologies provide a new way to study preeclampsia via accessing the earliest events in placental development. These advances include protocols that promote the conversion of totipotent human embryonic stem cells into trophoblast cells that can differentiate into typical trophoblast cell subpopulations in vitro and the use of induced pluripotent stem cells. The latter can be derived from the gestational tissues of affected and unaffected pregnancies. They may also retain etiologic genetic and epigenetic changes.

Duke Scholars

Author Danny J Schust Obstetrics and Gynecology, Reproductive Endocrinology & Infe ...