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In-vivo Imaging of Neuronal Differentiation and Function of Intracranially Implanted Induced Pluripotent Stem Cells (iPSCs) Using A Designer Receptor Exclusively Activated by A Designer Drug (DREADD)
https://repo.qst.go.jp/records/71549
https://repo.qst.go.jp/records/71549a310bfed-f68b-4388-9ad1-a639571d10e7
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2014-11-25 | |||||
| タイトル | ||||||
| タイトル | In-vivo Imaging of Neuronal Differentiation and Function of Intracranially Implanted Induced Pluripotent Stem Cells (iPSCs) Using A Designer Receptor Exclusively Activated by A Designer Drug (DREADD) | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Ji, Bin
× Ji, Bin× Kaneko, Hiroyuki× Minamimoto, Takafumi× Inoue, Haruhisa× Takeuchi, Hiroki× Kumata, Katsushi× Ming-Rong, Zhang× Aoki, Ichio× Seki, Chie× Ono, Maiko× Tokunaga, Masaki× Tsukamoto, Satoshi× Tanabe, Koji× Takahashi, Kazutoshi× Minamihisamatsu, Takeharu× Suhara, Tetsuya× Higuchi, Makoto× Ji, Bin× Minamimoto, Takafumi× Kumata, Katsushi× Ming-Rong, Zhang× Aoki, Ichio× Seki, Chie× Ono, Maiko× Tokunaga, Masaki× Tsukamoto, Satoshi× Minamihisamatsu, Takeharu× Suhara, Tetsuya× Higuchi, Makoto |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Induced pluripotent stem cells (iPSCs) provide a promising resource for cell replacement therapy in neurological diseases. In the present study, we have applied a designer receptor exclusively activated by a designer drug (DREADD) derived from human M4 muscarinic acetylcholine receptor (hM4D) and its synthetic ligand to in-vivo visualization of neuronal differentiation and function of iPSC-derived grafts implanted into the brain. We successfully captured expression of hM4D driven by neuron-specific Thy-1 promoter in newly-developed hM4D transgenic (hM4D Tg) mice with a 11C-labeled positron emission tomography (PET) ligand for hM4D. We also established iPSCs from a hM4D Tg mouse (hM4D-iPSC), and visualized time course of neuronal differentiation of grafts generated from these iPSCs in the living wild-type mouse brain by longitudinal PET imaging of hM4D with its specific radioligand. Quantitative assessment for cerebral blood flow using arterial spin labeling (ASL) MRI indicated suppression of neuronal activity by clozapine-N-oxide (CNO), an exclusive activator of hM4D, in hM4D Tg but not wild-type mice, in consistency with attenuation of locomotion behaviors. Furthermore, we found CNO-induced reduction of cerebral blood flow in areas associated with implantation of hM4D-iPSC-derived grafts by ASL-MRI of recipient mice. Our results support the utility of hM4D in combination with PET and ASL-MRI for in-vivo longitudinal monitoring of neuronal differentiation and functional manipulation of iPSC-derived implants in the brain. Since this technology is potentially applicable to humans, it would accelerate translational research and development of cell replacement therapy towards clinical trials. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Neuroscience meeting 2014 | |||||
| 発表年月日 | ||||||
| 日付 | 2014-11-21 | |||||
| 日付タイプ | Issued | |||||
