Extracellular Vesicles from Healthy Placenta Stem Cells Restored the Immune Licensing Function of Preeclamptic Placenta Stem Cells

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Preeclampsia (PE) contributes to pregnancy-related morbidity and mortality, with enhanced inflammation. Healthy placenta stem cells (P-MSCs) can be licensed into immune suppressor cells to mitigate inflammation. Since PE is associated with inflammation, the question is why the associated P-MSCs cannot suppress the response. PE P-MSCs have been shown to be dysfunctional with respect to decreased anti-inflammatory response, cell cycle dysregulation, and reduced production of immune suppressive cytokines. Aspirin (ASA) treatment partly reversed these dysfunctions via epigenetic reprogramming. We tested the hypothesis that extracellular vesicles (EVs) from healthy P-MSC could reset PE P-MSCs to a healthy phenotype, including cell cycle dysregulation and anti-inflammatory licensing. EVs from healthy MSCs were collected and the number of particles quantified. The isolated EVs were added to PE P-MSCs. Control cultures treated the PE P-MSCs with 1 mM ASA. The treated cells were assessed for the epigene regulator TDG and cell cycle linked CDK4, p21, and p53 by western blot, or assessed as third-party suppression in a one-way mixed lymphocyte reaction (MLR). EV- and ASA-treated PE P-MSC suppressed MLR, similar to healthy P-MSCs. However, an evaluation of p21, CDK4, p53, and TDG suggested that EVs impart a more stable restoration of PE P-MSCs when exposed to healthy EVs. This study provides insights into the method by which healthy P-MSCs can function to restore PE P-MSCs, and in vivo microenvironmental restoration.

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