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- Title
Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons.
- Authors
Ji-Yun Ko; Chang-Hwan Park; Hyun-Chul Koh; Youl-Hee Cho; Jee-Hong Kyhm; Young-Soo Kim; Inchul Lee; Yong-Sung Lee; Sang-Hun Lee
- Abstract
Human embryonic stem (hES) cells can be guided to differentiate into ventral midbrain-type neural precursor (NP) cells that proliferate in vitro by specific mitogens. We investigated the potential of these NP cells derived from hES cells (hES-NP) for the large-scale generation of human dopamine (DA) neurons for functional analyses and therapeutic applications. To address this, hES-NP cells were expanded in vitro for 1.5 months with six passages, and their proliferation and differentiation properties determined over the NP passages. Interestingly, the total hES-NP cell number was increased by > 2 × 104-folds over the in vitro period without alteration of phenotypic gene expression. They also sustained their differentiation capacity toward neuronal cells, exhibiting in vitro pre-synaptic DA neuronal functionality. Furthermore, the hES-NP cells can be cryopreserved without losing their proliferative and developmental potential. Upon transplantation into a Parkinson’s disease rat model, the multi-passaged hES-NP cells survived, integrated into the host striatum, and differentiated toward the neuronal cells expressing DA phenotypes. A significant reduction in the amphetamine-induced rotation score of Parkinson’s disease rats was observed by the cell transplantation. Taken together, these findings indicate that hES-NP cell expansion is exploitable for a large-scale generation of experimental and transplantable DA neurons of human-origin.
- Subjects
EMBRYONIC stem cells; CELLULAR therapy; PARKINSON'S disease; GENOTYPE-environment interaction; PHENOTYPES; CELL transplantation
- Publication
Journal of Neurochemistry, 2007, Vol 103, Issue 4, p1417
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.04898.x