Introduction: Mesenchymal stem cells (MSCs) derived from different sources are promising candidate for cell therapy in neurodegenerative diseases. MSCs can be used for transplantation in injured site of nervous system in differentiated and undifferentiated state. However, studies show that pre-differentiation of MSCs, before infusion into the brain have good efficiency in comparison to undifferentiated MSCs. Different methods utilized for neural differentiation of MSCs consist of combination of growth factors, small molecules and chemicals. Literature review: Studies show that chemical induction resulted in phonotypical change in cultured cells however, induction with molecules involved in neural development (growth factors, neurotrophins, cytokines and retinoic acid) and specific chemical reagents (ß-mercaptoethanol [BME], dimethyl sulfoxide [DMSO] and butylatedhydroxyanizole [BHA]). Chemical induction of MSCs characterized with fast induction of neuronal morphology and increased cell death. In fact, studies show that chemical reagents have cytotoxic and stressful effects on MSCs viability and morphology of the cells and these phonotypical neuronal like cells, have not functional neuronal characteristic. However, in comparison to chemical induction methods, developmental molecule-based method have steady state effect in morphologic changes and resulted in functional neural like cells. Recent studies show that embryonic cerebrospinal fluid (e-CSF) has important roles in neural development. Indeed, proteomic analysis revealed that precise combination of growth factors present in e-CSF. Interestingly, biological active molecules of e-CSF have similarity with components that utilized in MSCs neural induction. Our studies show that e-CSF induced neuronal like changes in MSCs. Similar to developmental molecules-based induction methods, e-CSF increased viability parallel with neural differentiation. Further analysis needed to optimize the neural induction effects of e-CSF