MESENCHYMAL STEM CELLS INFLUENCE TROPHOBLAST AND ENDOTHELIAL CELL FUNCTIONALITY IMPORTANT FOR PREVENTION OF PRE-ECLAMPSIA VIA A NOVEL ANTI-ANGIOGENIC PROTEIN, FKBPL
- Publisher:
- LIPPINCOTT WILLIAMS & WILKINS
- Publication Type:
- Conference Proceeding
- Citation:
- JOURNAL OF HYPERTENSION, 2018, 36, (&NA;), pp. E154-E154
- Issue Date:
- 2018-06-01
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Objective: Pre-eclampsia is a disorder affecting 5–6% of all pregnancies globally. It is characterised by the new onset of hypertension and proteinuria post 20 weeks gestation. Pre-eclampsia is a leading cause of morbidity and mortality in both mothers and children. Although the pathogenesis of pre-eclampsia is poorly understood, aberrant angiogenesis and inadequate trophoblast cell function have both been implicated. Mesenchymal Stem Cell (MSC)-based therapies have shown benefits in animal models of pre-eclampsia however, the underlying mechanisms are not well understood. FKBPL is a novel anti-angiogenic protein which has a critical role in developmental, physiological and pathological angiogenesis. In this study, our objective was to evaluate the effects of MSC–conditioned medium (MSC-CM) on migration and differentiation of trophoblast and endothelial cell lines under both normoxic and hypoxic conditions. The role of FKBPL signalling in these processes was also investigated.
Design and method: Human trophoblast (BeWo and Jar) and endothelial cells (HUVEC) were incubated in the presence of human bone marrow- derived MSC-CM, normal or serum free medium under normoxia (21% oxygen) or hypoxia (1% oxygen). The confluent cell monolayer was wounded and the percentage of wound closure assessed at 24 h. HUVEC were stained with Calcein prior to 6-hour incubation in the presence of MSC-CM, normal or serum free medium under normoxia or hypoxia. Tubule formation was assessed using Image J. FKBPL protein expression was evaluated using western blot analysis where cells were lysed in RIPA buffer before being subjected to western blotting and probed for FKBPL and GAPDH.
Results: MSC-CM promoted cell migration significantly in all three cell lines under both normoxia and hypoxia compared to normal medium (n = 6; p < 0.001). MSC-CM also significantly increased the formation of HUVEC tubule networks under both normoxia and hypoxia compared to normal medium. Furthermore, concomitant reduction in FKBPL protein expression was observed, demonstrating potential FKBPL's involvement in MSC-driven effects on trophoblast and endothelial cell functionality.
Conclusions: Our findings suggest that MSCs could be explored as potential preventative therapy for pre-eclampsia by ameliorating trophoblast and endothelial cell functionality, and that the mechanism is likely to involve a novel anti-angiogenic protein, FKBPL.
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