Dopamine release from transplanted neural stem cells

Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive.We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopaminelike neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantationofpNSC-DAn, (i ) pNSC-DAnretained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in the striatumboth in vitro (brain slices) andin vivo, as determined jointly by microdialysis-based HPLC and electrochemical carbon fiber electrodes; and (iii ) the rescued dopamine was released directly from the grafted pNSC-DAn (and not from injured original cells). Thus, pNSC-DAn grafts release and reuptake dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of- concept for human clinical translation.