Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Zdoi
10.1073/pnas.1408484111subject
Has Abstractpub_date
2014-11-04 00:00:00pages
15804-9issue
44eissn
0027-8424issn
1091-6490pii
1408484111journal_volume
111pub_type
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