Objective To investigate the role of cell-derived microparticles (MPs) in the differentiation of mesenchymal stem cells (MSCs) into neural stem cells.Methods MPs were isolated from human cerebrospinal fluid and primary MSCs were isolated from mouse bone marrow. After subculture, neural differentiation of MSCs was induced in a specialized medium with the presence of MPs. The number and length of cell processes were observed, and Western blot was used to measure the change in the expression of neuron-specific proteins.Results Compared with the neural induction medium group, the neural induction medium+MPs group had significantly longer cell processes (5.7±1.2 mm vs 2.2±0.4 mm, P<0.01) and a significantly higher number of cell processes (178.2±32 vs 94±12, P<0.01). The neural induction medium+MPs group had significantly higher expression of NSE, Nestin, and MAP-2 than the neural induction medium group (P<0.01).Conclusions MPs in cerebrospinal fluid can effectively promote the differentiation of MSCs into neural stem cells, which may provide new thoughts for stem cell transplantation in the treatment of neurological defects.