Human amniotic epithelial cells regulate osteoblast differentiation through the secretion of TGFβ1 and microRNA-34a-5p

: Since the beginning of the use of stem cells in tissue regenerative medicine, there has been a search for optimal sources of stem cells. Human amniotic epithelial cells (hAECs) are derived from human amnions, which are typically discarded as medical waste, but were recently found to include cells with trilineage differentiation potential in vitro. Previous study has focused on the osteogenic differentiation ability of hAECs as seed cells in bone regeneration; however, their paracrine effects on osteoblasts (OBs) are yet to be elucidated. In the present study, conditioned medium (CM) derived from hAECs was used to determine their paracrine effects on the human fetal OB cell line (hFOB1.19), and the potential bioactive factors involved in this process were investigated. The results suggested that hAEC-CM markedly promoted the proliferation, migration and osteogenic differentiation of hFOB1.19 cells. Expression of transforming growth factor β1 (TGFβ1) and microRNA 34a-5p (miR-34a-5p) were detected in hAECs. Furthermore, it was demonstrated that TGFβ1 and miR-34a-5p stimulated the differentiation of hFOB1.19 cells, and that TGFβ1 promoted cell migration. Moreover, the effects of hAEC-CM were downregulated following the depletion of either TGFβ1 or miR-34a-5p. These results demonstrated that hAECs promote OB differentiation through the secretion of TGFβ1 and miR-34a-5p, and that hAECs may be an optimal cell source in bone regenerative medicine.