Fibrocyte-Like Cells from Intrauterine Growth Restriction Placentas Have a Reduced Ability to Stimulate Angiogenesis

Abstract

Intrauterine growth restriction (IUGR) is a common complication of pregnancy whereby the fetus fails to achieve its genetic growth potential. Malformation of the placental vasculature is observed in IUGR and may be due to the development of the placenta in a chronically hypoxic environment. Recently, we identified that the predominant stromal cells in the angiogenic zones of the placenta are fibrocyte-like cells. The conditioned medium from fibrocyte-like cells (FcCM) has been shown to stimulate angiogenesis in vitro. Thus, we hypothesized that FcCM from IUGR cells would have a reduced ability to stimulate angiogenesis and that chronic hypoxia would decrease the ability of both normal and IUGR fibrocyte-like cells to stimulate angiogenesis. IUGR FcCM had a reduced ability to stimulate endothelial tubule-like structure formation and an increased ability to stimulate endothelial migration compared with normal FcCM. However, normal and IUGR FcCM produced in chronic hypoxia did not alter endothelial proliferation, migration, or tubule-like structure formation. IUGR FcCM was found to have reduced levels of the pro-angiogenic cytokine IL-8 and increased levels of the anti-angiogenic factors activin-A and pigment epithelium-derived growth factor. Thus, alterations in the ability of IUGR fibrocyte-like cells to stimulate angiogenesis may contribute to the development of vascular malformation in IUGR, but in vitro these changes cannot be attributed to a chronically hypoxic environment. (Am J Pathol 2013 http://dx

Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction

“…Abnormal vasculogenesis and angiogenesis are correlated with the impaired placental and fetal development observed in complicated pregnancies, such as IUGR [20]. Interestingly, in vitro studies showed that IUGR placental villous stromal cells altered ability to stimulate endothelial tubule-like structure formation and migration [37]. In addition, the imbalance between pro-and antiangiogenic factors is well documented in placentas and in maternal blood of IUGR and PE pregnancies, suggesting a role in their pathophysiology [38,39].…”

Morphological and Phenotypic Analyses of the Human Placenta Using Whole Mount Immunofluorescence1

“…While these methods have provided valuable insights into placental vascular biology, they lack the ability to provide detailed morphology in conjunction with phenotypic and dimensional information. Recent observations suggesting that several cell types within the placenta, including trophoblast cells, macrophages, and stromal cells, function together to promote placental development and angiogenesis [41][42][43] underscore the importance of being able to simultaneously examine all of these critical parameters. Using WMIF, we were able to overcome these limitations and obtain unparalleled images of the morphology, phenotype, and spatial orientation of several placental cell populations, including endothelial cells.…”