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

Abstract Spontaneous abortion (SA) is a syndrome with many origins. Among them, signal transduction or immune imbalance are major risk factors for SA. Wharton's jelly-mesenchymal stem cells (WJ-MSCs) are considered to be able to treat abortion. However, molecular signaling pathways and regulatory mechanisms to exert immune tolerance and maintain pregnancy of WJ-MSCs are poorly understood. We establish a rat abortion model using the subcutaneous injection of bromocriptine and inject WJ-MSCs into the rat through the tail vein on the 9th day of gestation. One experimental group included the cells treated with JAK/STAT inhibitor to test the contribution of this pathway. Here, we show that WJ-MSCs significantly lowered the rate of embryo resorption in the spontaneous abortion model. WJ-MSCs reduced Th1-related cytokines while increasing Th2 and Th3-related cytokines. Our observation that the ability of WJ-MSCs to prevent spontaneous abortion and alter cytokine profiles was lost upon inhibition of JAK/STAT signaling shows JAK/STAT signaling’s an important role to mediate SA. Together, these results reveal that WJ-MSCs prevent bromocriptine-induced spontaneous abortion in rats via JAK / STAT-mediated promotion of Th2 / Th3 cytokine responses and concurrent suppression of Th1 response and may offer a potential therapeutic target to prevent SA.