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dc.contributor.author남진우-
dc.date.accessioned2018-09-27T02:24:52Z-
dc.date.available2018-09-27T02:24:52Z-
dc.date.issued2016-08-
dc.identifier.citationBRAIN, v. 139, NO. 10, Page. 2722-2739en_US
dc.identifier.issn0006-8950-
dc.identifier.issn1460-2156-
dc.identifier.urihttps://academic.oup.com/brain/article/139/10/2722/2196669-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/76173-
dc.description.abstractThe original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson’s disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNAbinding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson’s disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells.en_US
dc.description.sponsorshipThis work was supported by a grant from the Medical Research Center (2008-0062287), funded by the National Research Foundation of Korea (NRF) of the Ministry of Science, ICT and Future Planning, Republic of Korea.en_US
dc.language.isoenen_US
dc.publisherOXFORD UNIV PRESSen_US
dc.subjectLIN28Aen_US
dc.subjectneural stem cell (NSC) cultureen_US
dc.subjectrepair capacityen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectcell transplantationen_US
dc.titleLIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson’s disease modelen_US
dc.typeArticleen_US
dc.relation.no10-
dc.relation.volume139-
dc.identifier.doi10.1093/brain/aww203-
dc.relation.page2722-2739-
dc.relation.journalBRAIN-
dc.contributor.googleauthorRhee, Yong-Hee-
dc.contributor.googleauthorKim, Tae-Ho-
dc.contributor.googleauthorJo, A.-Young-
dc.contributor.googleauthorChang, Mi-Yoon-
dc.contributor.googleauthorPark, Chang-Hwan-
dc.contributor.googleauthorKim, Sang-Mi-
dc.contributor.googleauthorSong, Jae-Jin-
dc.contributor.googleauthorOh, Sang-Min-
dc.contributor.googleauthorYi, Sang-Hoon-
dc.contributor.googleauthorNam, Jin-Wu-
dc.relation.code2016002542-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF NATURAL SCIENCES[S]-
dc.sector.departmentDEPARTMENT OF LIFE SCIENCE-
dc.identifier.pidjwnam-


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