3 years ago

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

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease
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 treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) 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 improved behavioral restoration, 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.

Graphical abstract

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Teaser

In this study, Lee and colleagues show that simple VC treatment during donor NSC preparation enhances cell therapeutic outcomes in a PD animal model, along with enriched midbrain DA neuron engraftment. The VC effect was achieved by a long-lasting epigenetic activation of midbrain DA neuron-specific developmental and phenotype gene expressions via DNA and repressive histone code demethylation.

Publisher URL: www.sciencedirect.com/science

DOI: S2213671117303740

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