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 transplantedcells themselves releasedopaminein vivo remains elusive. We and others have recently induced human embryonic stemcells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantation of pNSC-DAn, (i) pNSC-DAn retained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopaminerelease and reuptake were significantly rescued in the striatum both in vitro (brain slices) and in 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 dopaminein the striatumin vivo and alleviate PD symptoms inrats, providing proof-of-concept for human clinical translation.

Kang X, Xu H, Teng S, Zhang X, Deng Z, Zhou L, Zuo P, Liu B, Liu B, Wu Q, Wang L, Hu M, Dou H, Liu W, Zhu F, Li Q, Guo S, Gu J, Lei Q, Lü J, Mu Y, Jin M, Wang S, Jiang W, Liu K, Wang C, Li W*, Zhang K*, Zhou Z*. (2014) Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo. Proceedings of the National Academy of Sciences of the United States of America, 111(44):15804-15809.