Human Wharton's jelly‐derived mesenchymal stem cells prevent pregnancy loss in a rat by JAK/STAT‐mediated immunomodulation

Abstract

AbstractAimSpontaneous abortion (SA) is a multiple‐original syndrome with immune imbalance as one of its major risk factors. As Wharton's jelly‐mesenchymal stem cells (WJ‐MSCs) are considered to be able to prevent abortion, this study aims to explore the currently poorly understood underlining molecular signaling pathways and regulatory mechanisms of WJ‐MSCs in pregnancy maintenance.MethodsAbortion mode is established by subcutaneous injection of bromocriptine in rat on day 9 and abortion prevention is achieved by WJ‐MSCs injection via tail vein. WJ‐MSCs were cultured with/without the inhibitors of JAK/STAT or NF‐κB. The uterus was collected on the 14th day of gestation and the rate of embryo absorption was calculated. The expression of Th1/Th2/Th3 cytokines in decidual, placental tissue, and peripheral blood was analyzed.ResultsWJ‐MSCs treatment significantly reduced the abortion rate in bromocriptine‐treated pregnancy such that it was not significantly different from a normal pregnancy. JAK/STAT inhibition abolished pregnancy preserving effects of WJ‐MSCs but NF‐κB inhibition did not. The levels of Th1‐related cytokines and mRNA levels in the bromocriptine abortion model were significantly higher than the normal pregnancy group and ethanol control group, while levels of the Th2‐related cytokines and mRNA levels significantly decreased. WJ‐MSCs transfusion into the abortion model restored cytokine profiles such that they were not significantly different from the normal pregnancy group and ethanol control group. JAK/STAT inhibition of WJ‐MSCs prevented their effect on cytokine and mRNA levels, but NF‐κB inhibition did not.ConclusionsWJ‐MSCs significantly lower the rate of embryo resorption of spontaneous abortion by reducing Th1‐related cytokines while increasing Th2 and Th3‐related cytokines in JAK/STAT‐dependent manner.