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 m...
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Elsevier
2017-10-01
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| Series: | Stem Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117303740 |
| _version_ | 1798046119952908288 |
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| author | Noviana Wulansari Eun-Hee Kim Yanuar Alan Sulistio Yong-Hee Rhee Jae-Jin Song Sang-Hun Lee |
| author_facet | Noviana Wulansari Eun-Hee Kim Yanuar Alan Sulistio Yong-Hee Rhee Jae-Jin Song Sang-Hun Lee |
| author_sort | Noviana Wulansari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:32:22Z |
| format | Article |
| id | doaj.art-4588dc8a00bf4dff995c2d904e495007 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-11T23:32:22Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-4588dc8a00bf4dff995c2d904e4950072022-12-22T03:57:06ZengElsevierStem Cell Reports2213-67112017-10-01941192120610.1016/j.stemcr.2017.08.017Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's DiseaseNoviana Wulansari0Eun-Hee Kim1Yanuar Alan Sulistio2Yong-Hee Rhee3Jae-Jin Song4Sang-Hun Lee5Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaDepartment of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaDepartment of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaDepartment of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaDepartment of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaDepartment of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, KoreaCultured 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.http://www.sciencedirect.com/science/article/pii/S2213671117303740neural stem cellventral midbrainvitamin CepigeneticParkinson's diseasecell transplantation |
| spellingShingle | Noviana Wulansari Eun-Hee Kim Yanuar Alan Sulistio Yong-Hee Rhee Jae-Jin Song Sang-Hun Lee Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Stem Cell Reports neural stem cell ventral midbrain vitamin C epigenetic Parkinson's disease cell transplantation |
| title | Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease |
| title_full | Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease |
| title_fullStr | Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease |
| title_full_unstemmed | Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease |
| title_short | Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease |
| title_sort | vitamin c induced epigenetic modifications in donor nscs establish midbrain marker expressions critical for cell based therapy in parkinson s disease |
| topic | neural stem cell ventral midbrain vitamin C epigenetic Parkinson's disease cell transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117303740 |
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