論文 - 詳細
| RRC ID | 6795 |
|---|---|
| 著者 | Vazin T, Chen J, Spivak CE, Amable R, Gabitzsch E, Lee CT, Lupica CR, Freed WJ. |
| タイトル | Dopaminergic neurons derived from BG01V2, a variant of human embryonic stem cell line BG01. |
| ジャーナル | Restor Neurol Neurosci |
| Abstract |
BACKGROUND AND PURPOSE:Human embryonic stem cells (hESC) are considered a renewable source of dopamine producing neurons, and are of particular interest for their potential clinical use in Parkinson's disease. In this study, we characterized human dopaminergic neurons generated by stromal-derived inducing activity (SDIA) from BG01V2, a strain of human embryonic stem cell line, BG01, characterized by a chromosome 17 trisomy. Similar chromosomal changes have been repeatedly observed in hESC cultures in different laboratories, indicating the importance of chromosome 17 for growth and adaptation of hESC to culture. METHODS:We investigated in vitro proliferation of differentiating cells using a BrDU incorporation assay, and monitored the cell population in long term cultures. Despite the cytogenetic abnormality, TH+ neurons were postmitotic at all stages of differentiation. After 30 days of differentiation, cell division ceased in 91% of the overall population of cells in the culture, indicating intact cell cycle regulation. RESULTS:Expression of midbrain specific marker genes (Otx2, Pax5, Msx-1) showed differentiation of hESC-derived neural progenitor cells into midbrain specific dopamine neurons. These neurons expressed the dopamine transporter (DAT), and displayed functional DAT activity and electrical excitability. CONCLUSIONS:TH+ cells derived from the BG01V2 hESC line using SDIA are postmitotic and have functional characteristics of normal dopaminergic neurons. |
| 巻・号 | 26(6) |
| ページ | 447-58 |
| 公開日 | 2008-1-1 |
| PMID | 19096132 |
| PMC | PMC2696893 |
| MeSH | Actins / metabolism Bromodeoxyuridine / metabolism Cell Differentiation / physiology* Cell Line Cell Proliferation Chromosomes, Human, Pair 17 Cocaine / analogs & derivatives Cocaine / pharmacokinetics Coculture Techniques Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / metabolism Embryonic Stem Cells / physiology* Humans Membrane Potentials / physiology Microtubule-Associated Proteins / metabolism Nerve Tissue Proteins / metabolism Neurons / physiology* Otx Transcription Factors / metabolism Patch-Clamp Techniques / methods Protein Binding / drug effects Time Factors Tritium / pharmacokinetics Tyrosine 3-Monooxygenase / metabolism |
| IF | 2.378 |
| 引用数 | 8 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-G2/PA6(RCB1127) |