骨髄不全におけるCXCR4陽性造血幹細胞を標的とした新規治療法の開発

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Author: 中尾, 眞二ほか

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Publication date: 2017-05-31

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Note (General)：: 金沢大学医薬保健研究域医学系余剰造血幹前駆細胞（HSPC）のマーカーであるCXCR4陽性のHSCPを活性化できれば、再生不良性貧血（再不貧）患者の造血機能を改善させられる可能性がある。免疫不全マウスの骨髄内にヒトCD34(+)細胞を移植したところ、3.3-20.4%のヒトCD45陽性細胞の再生を確認...

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https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15K15360/

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Material Type: 文書・図像類
Title: 骨髄不全におけるCXCR4陽性造血幹細胞を標的とした新規治療法の開発
Author/Editor: 中尾, 眞二
Nakao, Shinji
Author Heading: 中尾, 眞二
Nakao, Shinji
Publication Date: 2017-05-31
Publication Date (W3CDTF): 2017-05-31
Alternative Title: Development of a new therapy targeting CXCR4+ hematopoietic stem cells in patients with bone marrow failure
Periodical title: 平成28(2016)年度科学研究費補助金挑戦的萌芽研究研究成果報告書 = 2016 Fiscal Year Final Research Report
No. or year of volume/issue: 2015-04-01 - 2017-03-31
Volume: 2015-04-01 - 2017-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: 再生不良性貧血
造血幹前駆細胞
CXCR4
BRGSマウス
iPS細胞
6pLOH
Target Audience: 一般
Note (General): 金沢大学医薬保健研究域医学系
余剰造血幹前駆細胞（HSPC）のマーカーであるCXCR4陽性のHSCPを活性化できれば、再生不良性貧血（再不貧）患者の造血機能を改善させられる可能性がある。免疫不全マウスの骨髄内にヒトCD34(+)細胞を移植したところ、3.3-20.4%のヒトCD45陽性細胞の再生を確認した。６pLOH陽性の再不貧患者単球由来iPS細胞からHSPCを誘導し、同じマウスに移植したところ、患者体内で優勢であった6pLOH(+)HSPCのCXCR4(+)細胞割合(平均10.2%)は野生型（50.7％）に比べて有意に低値であった。野生型CXCR4(+)HSPCをin vivoで活性化させる方法を現在検討中である。
A chemokine receptor CXCR4 is preferentially expressed by redundant hematopoietic stem/progenitor cells (HSPCs) that do not contribute to hematopoiesis. Stimulation of residual CXCR4(+) HSPCs may restore hematopoietic function of patients with acquired aplastic anemia (AA). First, we optimized method of engrafting an immune-deficient mouse (BRGS mouse) with cord-blood CD34(+) cells using intra-bone marrow injection, and confirmed the presence of human CD45(+) cells that accounted for 3.3-20.4% of the various tissue-derived cells. Next, we induced HSPCs from iPS cells that were generated from monocytes of AA patients possessing 6pLOH(+) leukocytes, which were predominant in the patients’ blood, as a result of uniparental disomy, and injected the HSPCs to the same mice. Regenerating human 6pLOH(+)CD34(+) cells in the mice expressed CXCR4 to a significantly lesser degree (mean 10.2%) than did 6pLOH(-)CD34(+) cells. We are currently exploring a method to activate CXCR4(+) HSPCs in vivo.
研究課題/領域番号:15K15360, 研究期間(年度):2015-04-01 - 2017-03-31
DOI: 10.24517/00051101
Source: https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44760&item_no=1&attribute_id=26&file_no=1
https://kanazawa-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=44760&item_no=1&attribute_id=26&file_no=1
Access Restrictions: 限定公開
Rights (production): CC BY-NC-ND
Related Material: https://kaken.nii.ac.jp/search/?qm=70217660
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15K15360/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-15K15360/15K15360seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA