Impact of immunosuppression on endothelial progenitor cell capacity in pregnancy

Objective:

Pregnancy is no longer unattainable for women with organ transplants but immunosuppression must be maintained throughout pregnancy. Women after transplantation have a higher risk for preeclampsia, a severe hypertensive disorder. We have previously described alterations of endothelial-colony forming cells (ECFC), a subtype of endothelial progenitor cells, from preeclamptic patients. These cells have a high proliferative potential and are involved in angiogenesis, vascular repair and uterine remodeling during pregnancy. Here we studied the impact of organ transplantation and calcineurin inhibitors (tacrolimus and cyclosporine) on fetal ECFC characteristics.

Methods:

ECFCs were isolated from umbilical cord blood of uncomplicated pregnancies and treated with serum obtained from female kidney transplant patients or healthy, age matched controls (2,5% vol) or different doses of tacrolimus or cyclosporine (0,01 – 10µM). Cell viability, proliferation, migration, chemotaxis and angiogenesis capacity were evaluated in vitro.

Results:

Serum of women with kidney transplants impaired ECFC proliferation compared to controls (doubling time: 157h vs. 58h; p < 0,0001). Tacrolimus and cyclosporine led to a dose dependent decrease of proliferation, migration, chemotaxis ability and angiogenesis and enhanced apoptosis of ECFCs.

Summary:

Calcineurin inhibitors reduce the functional capacity of cord blood derived ECFCs. These findings suggest that immunosuppression can contribute to the increased risk of preeclampsia after organ transplantation by promoting endothelial dysfunction. An evaluation of potential reversing effects of statins or vitamin D is currently under way.