Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Abstract

Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.