論文 - 詳細
| RRC ID | 85418 |
|---|---|
| 著者 | Nakagomi T, Nakano-Doi A, Kubo S, Sawano T, Kuramoto Y, Yamahara K, Matsuyama T, Takagi T, Doe N, Yoshimura S. |
| タイトル | Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke. |
| ジャーナル | Stem Cells Transl Med |
| Abstract |
We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients. |
| 巻・号 | 12(6) |
| ページ | 400-414 |
| 公開日 | 2023-6-15 |
| DOI | 10.1093/stcltm/szad031 |
| PII | 7177376 |
| PMID | 37221140 |
| PMC | PMC10267578 |
| MeSH | Animals Brain / pathology Brain Ischemia* / metabolism Brain Ischemia* / therapy Humans Mice Mice, Transgenic Multipotent Stem Cells Neural Stem Cells* Neurogenesis / physiology Stroke* / pathology Stroke* / therapy |
| IF | 6.429 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC06355 |