112 9

LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson’s disease model

Title
LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson’s disease model
Author
남진우
Keywords
LIN28A; neural stem cell (NSC) culture; repair capacity; Parkinson’s disease; cell transplantation
Issue Date
2016-08
Publisher
OXFORD UNIV PRESS
Citation
BRAIN, v. 139, NO. 10, Page. 2722-2739
Abstract
The 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.
URI
https://academic.oup.com/brain/article/139/10/2722/2196669https://repository.hanyang.ac.kr/handle/20.500.11754/76173
ISSN
0006-8950; 1460-2156
DOI
10.1093/brain/aww203
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
Files in This Item:
LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson's disease model.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE