F Calcaterra1, A Taddeo2, E Colombo1, M Cappelletti1, A Martinelli3, S Calabrese3, D Mavilio1, I Cetin3, S Della Bella4. 1. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Italy; Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, MI, Italy. 2. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Italy. 3. Center for Fetal Research "Giorgio Pardi", Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Italy. 4. Department of Medical Biotechnologies and Translational Medicine, University of Milan, Italy; Lab of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, MI, Italy. Electronic address: silvia.dellabella@unimi.it.
Abstract
INTRODUCTION: Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion. METHODS: Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45(dim)/CD34+ / KDR+ cells by flow cytometry. Plasmatic cytokines were measured by ELISA. RESULTS: We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment. CONCLUSIONS: EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.
INTRODUCTION: Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion. METHODS: Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45(dim)/CD34+ / KDR+ cells by flow cytometry. Plasmatic cytokines were measured by ELISA. RESULTS: We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment. CONCLUSIONS: EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.