Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical For Cell-Based Therapy in Parkinson's Disease

Title
Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical For Cell-Based Therapy in Parkinson's Disease
Author
Noviana Wulansari
Advisor(s)
Sang Hun Lee
Issue Date
2018-08
Publisher
한양대학교
Degree
Doctor
Abstract
Cultured neural stem/precursor cells(NSCs) are regarded as a potential systematic cell source to treat Parkinson’s disease(PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that vitamin C(VC) potentiates the therapeutic capacity of NSCs cultured from the ventral midbrain(VM), via enhancement of DA neuronal yield, survival, neuronal function, and midbrain-specific marker expression. VC acted by upregulating a series of midbrain DA neuron–specific developmental and phenotype genes via DNA hydroxymethylation/demethylation and repressive histone code (H3K9m3, H3K27m3) demethylation at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in remarkable behavioral improvement, along with enriched DA neuron engraftment, which faithfully expressed midbrain-specific markers in PD model rats. These results indicate that VC treatment to donor NSCs could be a simple, efficient, and safe therapeutic strategy for PD in the future.
URI
http://dcollection.hanyang.ac.kr/common/orgView/000000106343http://repository.hanyang.ac.kr/handle/20.500.11754/76076
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Ph.D.)
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

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

BROWSE