Cell- and size-specific analysis of placental extracellular vesicles in maternal plasma and pre-eclampsia

Despite decades of investigation, we cannot predict, prevent, or adequately treat the most common and deadly complications of pregnancy, including pre-eclampsia (pregnancy-induced hypertension). The current working hypothesis for the repeated failures of several multicenter studies that measured a wide variety of biomarkers is common pregnancy complications like pre-eclampsia are most likely heterogeneous syndromes with various etiologies; therefore, no combination of blood-based biomarkers will provide predictive power. Although the clinical syndrome of pre-eclampsia may have various causes, the current dogma is most cases share similar placental pathology, including accelerated chorionic villous maturation and an increased frequency of malperfusion-related infarctions. This pathology is thought to begin in the late first trimester of pregnancy. The challenge has been to develop an approach to monitor placental health in vivo. New contrast-enhanced imaging studies of blood flow to the placenta are providing insights, but rapid liquid-based assays using maternal blood would be more cost-effective. Recently, there has been a growing interest in placental extracellular vesicles (EVs) to determine if these complex lipid-based spheres involved in intercellular communication offer clues to the early pathophysiology of placental damage. Most EVs are nanoscale-sized exosomes (∼60–120 nm) that retain cell-specific plasma membrane surface markers. Their concentration, composition, and relative size distribution may provide clinical predictive power, but more investigation is needed. A major obstacle to advancement in this field has been the lack of EV imaging and isolation assays that can provide both cell- and size-specificity. Nanoscale multiplex high-resolution flow cytometry being developed in a number of laboratories may provide a solution. It is a potential means to quantitate both cell- and size-specific EVs from various cell sources, including the placenta.