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

摘要

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 healthin 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.