Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia

Abstract

Amniotic fluid surrounding the developing fetus is a complex biological fluid rich in metabolically active bio‐factors. The presence of extracellular vesicles (EVs) in amniotic fluid has been mainly related to foetal urine. We here characterized EVs from term amniotic fluid in terms of surface marker expression using different orthogonal techniques. EVs appeared to be a heterogeneous population expressing markers of renal, placental, epithelial and stem cells. Moreover, we compared amniotic fluid EVs from normal pregnancies with those of preeclampsia, a hypertensive disorder affecting up to 8% of pregnancies worldwide. An increase of CD105 (endoglin) expressing EVs was observed in preeclamptic amniotic fluid by bead‐based cytofluorimetric analysis, and further confirmed using a chip‐based analysis. HLA‐G, a typical placental marker, was not co‐expressed by the majority of CD105+ EVs, in analogy with amniotic fluid stromal cell derived‐EVs. At a functional level, preeclampsia‐derived EVs, but not normal pregnancy EVs, showed an antiangiogenic effect, possibly due to the decoy effect of endoglin. Our results provide a characterization of term amniotic fluid‐EVs, supporting their origin from foetal and placental cells. In preeclampsia, the observed antiangiogenic characteristics of amniotic fluid‐EVs may reflect the hypoxic and antiangiogenic microenvironment and could possibly impact on the developing fetus or on the surrounding foetal membranes.

Human amniotic fluid derived extracellular vesicles attenuate T cell immune response

“…EVs derived from bone marrow MSCs can induce T cell apoptosis and increase T regulatory: T effector cell ratio ( ( 38 ). EVs derived from AF have previously been shown to modulate lung tissue structure and vascularization ( 6 , 7 ); however, this is the first time AF-EVs have been shown to affect immune cell activity. Together, this data further demonstrates that AF is a promising and novel source for therapeutic EVs and depicts a potential mechanism of action through the ability to alter the T-cell response.…”

“…AF is a rich source of EVs that have been characterized to express EV specific tetraspanins CD9, CD63, and CD81, and to carry immune modulatory and anti-inflammatory RNA and protein cargo ( 6 , 7 ). AF-derived EVs (AF-EVs) can regulate angiogenesis and are capable of altering lung tissue structure ( 6 , 7 ).…”

“…AF is a rich source of EVs that have been characterized to express EV specific tetraspanins CD9, CD63, and CD81, and to carry immune modulatory and anti-inflammatory RNA and protein cargo ( 6 , 7 ). AF-derived EVs (AF-EVs) can regulate angiogenesis and are capable of altering lung tissue structure ( 6 , 7 ). Additionally, AF-derived treatments have recently entered the clinic as a novel therapeutic for the treatment of COVID-19 long haulers and COVID-19 induced acute respiratory distress syndrome and inflammation ( 8 , 9 ).…”

“…AF-EVs consist of EVs secreted from various cell sources in the surrounding perinatal environment, including AFSCs, but also placental cells ( 7 ). Perinatal cells from various tissues and their extracellular vesicles have been shown to suppress immune cell activity in both innate and adaptive immune systems ( 19 ).…”

Overview and Update on Extracellular Vesicles: Considerations on Exosomes and Their Application in Modern Medicine

“…EVs cargo can be affected by changes in gene expression resulting from environmental cues such as oxygen levels or inflammation. Based on surface marker expression, Gebara et al [ 147 ] found that amniotic fluid-derived EVs showed a heterogeneous origin; vesicles expressed markers of fetal, placental cells, and also mesenchymal and stem cells markers. Investigations on tetraspanin marker expression profiles in individual EVs have evidenced seven subpopulations.…”