Previous Studies have shown that mesenchymal stern cells (MSCs) enhance repair following injury or degenerative diseases in the central nervous system, but the underlying mechanisms remain Unclear. The present Study investigated the functional relationship between MSCs and neural stem cells (NSCs) Using co-culture systems. Results demonstrated that MSCs promoted outgrowth and guided directional extension of NSC-derived neurites. The majority of neurites were oriented parallel along the MSC axis. Stripe assay results indicated that cell adhesion molecule and extracellular matrix, such as N-cadherin, fibronectin, and laminin, contributed to this effect. Furthermore, Western blot analysis revealed that phosphorylation of cAMP response element-binding protein (CREB) increased during this process. In addition MSCs promoted differentiation of NSCs into oligodendrocytes via secreted Soluble factors., The oligodendrocytes were distributed along the MSC Surface in a regular pattern. This Study demonstrated that MSC transplantation could be a potential strategy for treating central nervous system injuries. (C) 2009 Elsevier Inc. All rights reserved.