(287) Aspirin restores preeclamptic placental mesenchymal stem cells for licensing to immune suppressor cells

Objective: Preeclampsia (PE) affects 2-8% of pregnancies globally and can lead to serious complications. Pregnancy depends on the maternal immune system’s ability to tolerate the allogeneic fetus.Transforming growth factor β (TGF-β) plays a role in this process. MSCs are normally licensed, or educated, by inflammation to act as anti-inflammatory cells. Omics studies in our group identified increased TGF-β signaling when PE-derived placental mesenchymal stem cells (PE-MSCs) were treated with aspirin (ASA). We tested the hypothesis that PE-MSCs restored with ASA can mitigate inflammation.

Study Design: We obtained placentas from singleton pregnancies at or near term from healthy and PE patients; excluding subjects with abnormal placentas, infections or preexisting medical comorbidities. MSC identity was confirmed by flow cytometry and multilineage differentiation capacity. We tested the density of TGF-β receptor and amount of active cytokine induced by ASA treatment. Immune suppression by ASA-treated MSCs was assessed in a 2-way mixed lymphocyte reaction (MLR) in which PE-MSCs were added as third-party cells after ASA treatment.

Results: ASA increased TGF-β receptor density, with untreated PE-MSCs expressing undetectable TGF-β receptor and ASA treatment yielding strong expression. ASA treatment led to a >100 fold increase in active TGF-β cytokine production. Functionally, the ASA-treated PE-MSCs were 30% more effective at suppressing T-cell proliferation than untreated PE-MSCs.

Conclusion: The data illustrate a possible mechanism through which ASA enhances PE-MSCs’ anti-inflammatory capacity through TGF-β. Specifically, ASA treatment yields increased levels of active TGF-β cytokine with concomitant increased TGF-β receptor expression, suggesting that not only are the MSCs producing more of this anti-inflammatory cytokine, but are more susceptible to it as well. The findings support our hypothesis that the newly licensed ASA-treated PE-MSCs can mitigate inflammation in subjects with PE to decrease the clinical phenotype.