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Customizing EV-CATCHER to Purify Placental Extracellular Vesicles from Maternal Plasma to Detect Placental
Megan I Mitchell1,2,3, Marwa Khalil2,3, Iddo Z Ben-Dov4
1Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.
International Journal of Molecular Sciences
|May 25, 2024
Summary
Researchers developed a new method to detect Placenta Accreta Spectrum (PAS) using placental extracellular vesicles (EVs) and their microRNA (miRNA) profiles. This molecular approach shows promise for earlier and more accurate non-invasive diagnosis of this dangerous pregnancy complication.
Area of Science:
- Obstetrics and Gynecology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Placenta Accreta Spectrum (PAS) is a severe obstetric complication with high morbidity and mortality, often diagnosed late.
- Current diagnostic methods like ultrasound and MRI have limitations, leading to potential misdiagnosis and undiagnosed cases.
- Non-invasive molecular detection of PAS using circulating biomarkers, specifically placental extracellular vesicles (EVs) and their miRNA content, remains underexplored.
Purpose of the Study:
- To develop and evaluate a novel method for non-invasive molecular detection of Placenta Accreta Spectrum (PAS).
- To purify placental EVs from maternal plasma using a placental alkaline phosphatase (PLAP)-targeting antibody.
- To compare miRNA expression profiles in placental EVs between women with placenta percreta (PAS) and placenta previa.
Main Methods:
- Customized an ultra-sensitive immuno-purification assay (EV-CATCHER) using a monoclonal antibody against placental alkaline phosphatase (PLAP).
- Purified placental EVs from maternal plasma of women with placenta percreta (cases, n=16) and placenta previa (controls, n=16).
- Analyzed miRNA expression profiles of purified PLAP+ EVs using next-generation sequencing.
Main Results:
- Identified 40 differentially expressed miRNAs in placental EVs between placenta percreta and placenta previa cases.
- Preliminary pathway enrichment analysis suggested roles for differentially expressed miRNAs in cellular invasion and motility.
- The EV-CATCHER assay successfully purified placental EVs expressing PLAP from maternal plasma.
Conclusions:
- Circulating placental EVs and their miRNA cargo hold potential as non-invasive biomarkers for Placenta Accreta Spectrum (PAS).
- The developed PLAP+ EV purification method shows promise for molecular diagnostics of PAS.
- Further investigation is warranted to validate these findings and explore the functional roles of identified miRNAs in PAS pathogenesis.
