AbstractBackgroundIn recent years, the ability of neural stem cells (NSCs) transplantation to treat Parkinson's disease (PD) has attracted attention. However, it is still a challenge to promote the migration of NSCs to the lesion site and their directional differentiation into dopaminergic neurons in PD. C‐C motif chemokine ligand 5 (CCL5) and C‐C motif chemokine receptor 5 (CCR5) are expressed in the brain and are important regulators of cell migration. It has been reported that ethyl stearate (PubChem CID: 8122) has a protective effect in 6‐OHDA‐induced PD rats.MethodsParkinson's disease rats were injected with 6‐hydroxydopamine (6‐OHDA) into the right substantia nigra, and striatum followed by 8 μL of an NSC cell suspension containing 100 μM ethyl stearate and 8 × 105cells in the right striatum. The effect of transplantation NSCs combined with ethyl stearate was assessed by evaluating apomorphine (APO)‐induced turning behavior and performance in the pole test. Quantitative real‐time reverse transcription–polymerase chain reaction (qRT‐PCR), Western blotting (WB), and immunofluorescence staining were also performed.ResultsNSCs transplantation combined with ethyl stearate ameliorated the behavioral deficits of PD rats. PD rats that received transplantation NSCs combined with ethyl stearate exhibited increased expression of tyrosine hydroxylase (TH) and an increased number of green fluorescent protein (GFP)‐positive cells. Furthermore, GFP‐positive cells migrated into the substantia nigra and differentiated into dopaminergic neurons. The expression of CCL5 and CCR5 was significantly increased after transplantation NSCs combined with ethyl stearate.ConclusionsThese findings suggest that NSCs transplantation combined with ethyl stearate can improve the motor behavioral performance of PD rats by promoting NSCs migration from the striatum to the substantia nigra via CCL5/CCR5 and promoting the differentiation of NSCs into dopaminergic neurons.