Umbilical cord mesenchymal stem cells protect against obstetric deep venous thrombosis in rats by suppressing ferroptosis

The administration of UCMSCs into pregnant rats diagnosed with DVT notably led to a greater degree of angiogenesis, alleviated coagulation, inflammation, and ferroptosis, and ameliorated the pregnancy outcomes. In vitro, erastin induced typical features related to ferroptosis. UCMSC-conditioned medium (UC-CM) effectively enhanced the capacity of dysfunctional endothelial cells to undergo proliferation, migration, invasion, and the formation of vessel-like structures, and normalized the levels of reactive oxygen species and malondialdehyde. The analysis of KEGG pathway enrichment revealed that the signaling pathway associated with ferroptosis in the thrombosed tissues of rats in the UCMSC group markedly suppressed. The levels of arachidonate-15-lipoxygenase (ALOX15), a marker related to ferroptosis, was significantly downregulated in both thrombosed tissues and endothelial cells sorted out from these tissues after UCMSC transplantation. Furthermore, the function of ALOX15 was verified in vitro and in vivo. In conclusion, this study suggested that UCMSCs mitigated the inflammation levels, facilitated recanalization, and improved pregnancy outcomes in cases of obstetric DVT by mitigating ferroptosis within endothelial cells.