期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：44
页码：15804-15809
DOI：10.1073/pnas.1408484111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceWith a combination of HPLC and carbon fiber electrodes, we demonstrate that grafted neural stem cells directly release dopamine in the damaged striatum in vivo and partially rescue a Parkinson's disease (PD) model. (i) Primitive neural stem cell-dopamine-like neuron (pNSC-DAn) retained tyrosine hydroxylase expression and reduced the PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in striatum in vitro (brain slices) and in vivo, as determined jointly by microdialysis-based HPLC and electrochemical micro-carbon fiber electrodes; and (iii) the rescued dopamine was released directly from the grafted pNSC-DAn (not from the 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. 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 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 dopamine release 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 dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of-concept for human clinical translation.
关键词：dopamine ; Parkinson's disease ; striatum in vivo ; neural stem cells ; CFE
