Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation in vitro

In human chorionic villi, numerous macrophages, so-called Hofbauer cells, a re located adjacent to trophoblasts. To determine the role of the macrophag es in the proliferation and differentiation of trophoblasts, cytotrophoblas t cells were cultured in serum-free culture-conditioned media of villous ma crophages (VMCM), peritoneal macrophages (PMCM), and villous fibroblasts (V FCM). In VMCM, proliferation of cytotrophoblast cells was detected at 24 h by immunocytochemistry with Ki-67-antibody. A large number (P < 0.001) of m ultinucleated syncytia was formed in VMCM. In VMCM, cytotrophoblast cell fu sion was completed by 96 h, which coincided with the peak of hCG secretion and initiation of human placental lactogen (hPL) release. Levels of hCG (P < 0.001) and hPL (P < 0.001) secretion from syncytial cells were significan tly higher in VMCM than in PMCM or in VFCM. Concentrations of macrophage co lony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEG F) analyzed by ELISA were greater in VMCM than in PMCM or in VFCM, whereas monocyte chemoattractant protein-1 (MCP-1) concentration was high in PMCM. The expression patterns of M-CSF, VEGF, and MCP-1 in villous macrophages an d peritoneal macrophages by reverse transcriptase-polymerase chain reaction were similar to their secretion patterns. Thus, villous macrophages have a greater ability to stimulate hCG and hPL secretion than do peritoneal macr ophages. This study suggests that macrophages within the villous stroma may stimulate the growth and differentiation of trophoblasts through their sec reted substances.