Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons |
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Authors: | Ko Ji-Yun Park Chang-Hwan Koh Hyun-Chul Cho Youl-Hee Kyhm Jee-Hong Kim Young-Soo Lee Inchul Lee Yong-Sung Lee Sang-Hun |
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Affiliation: | Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, South Korea; Department of Microbiology, College of Medicine, Hanyang University, Seoul, South Korea; Department of Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea; Department of Medical Genetics, College of Medicine, Hanyang University, Seoul, South Korea; Institute of Mental Health, Hanyang University, Seoul, South Korea; Cell Therapy Research Center, Hanyang University, Seoul, South Korea; Department of Neurosurgery, Hanyang University Medical Center, Seoul, South Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea |
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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. |
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Keywords: | dopamine neurons human embryonic stem cells neural precursor cell Parkinson's disease |
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