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Objective: To investigate whether promotion of neuronal differentiation of human umbilical cord mesenchymal stem cells (HUMSCs) by progesterone (PROG) involves changes in brain-derived neurotrophic factor (BDNF) levels. Methods: We used rat brain tissue extracts to mimic the brain microenvironment. Quantitative sandwich enzyme-linked immunosorbent assay was performed to measure levels of BDNF in cultured medium with or without PROG. Results: Progesterone increased levels of BDNF in HUMSCs. Conclusion: Progesterone enhancement of brain-derived neurotrophic factor levels may be involved in PROG activated-pathways to promote neuronal differentiation of HUMSCs. [ABSTRACT FROM AUTHOR]