臍帯血移植細胞の脳内浸潤からみた脳性麻痺治療メカニズムの解明

从脐带血移植细胞脑内浸润角度阐明脑瘫治疗机制

• 批准号: 22K07915
• 负责人: 津田 雅之
• 金额: $ 2.66万
• 依托单位: Kochi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K07915/
• 关键词: 臍帯血; 脳性麻痺; 血液脳関門

脳性麻痺に対する新規治療法として本学医学部附属病院で実施されている自家臍帯血移植治療の治癒メカニズムを明らかにするため、新生仔脳虚血再灌流障害モデルを改良した独自の脳性麻痺モデルを開発し解析を行ってきた。生後9日齢の免疫不全マウスを用いてモデルマウスを作製し、3週間後にヒト臍帯血細胞を静脈投与すると、内在性の神経幹細胞が賦活化し、分化した神経前駆細胞は増殖しながら損傷部位に誘導されることが明らかとなった。移植細胞の脳実質内への浸潤は、神経幹/前駆細胞の賦活化による脳障害の改善に向けた最初の重要なステップと考えられる。血管に投与された臍帯血細胞が血液脳関門を超えて、どのように脳実質内に浸潤するのかを調べることにした。血液脳関門の破綻の状態を調べるため、脳損傷24時間と3週間後の脳性麻痺モデルマウスの血管にエバンスブルーを投与し、脳実質内への漏出量を定量した。脳損傷24時間の急性期では、障害側で顕著な漏出が観察されたが、3週間後の慢性期においては、漏出は観察されるもののその程度は低く、正常側と比較して有為な差は認められなかった。次に、血液脳関門の形態を解析するため、ペリサイトとアストロサイトの免疫染色を行った。ペリサイトのマーカーとしてPDGFRβを用いた。脳損傷24時間後の障害部位付近にはペリサイトのシグナルは観察されなかったが、3週間後には観察されるようになった。さらに、脳血管を取り囲むアストロサイトの足突起のマーカーであるアクアポリン4と血管を可視化できる蛍光標識トマトレクチンを用いて、脳切片上でそれらの局在を調べた。その結果、脳損傷3週間後においても共局在は観察されず、血管は足突起に覆われない状態で存在していた。これらのことから、臍帯血細胞の移植時期である脳損傷3週間後の慢性期における血液脳関門は急性期から回復しつつあるものの、その破綻は続いていることが明らかとなった。

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项目成果

Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study

• DOI: 10.1016/j.braindev.2022.08.004
• 发表时间: 2022-11-05
• 期刊: BRAIN & DEVELOPMENT
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• 作者: Kikuchi，Hiroaki;Saitoh，Shiho;Fujieda，Mikiya
• 通讯作者: Fujieda，Mikiya

A novel subpopulation of B1 B cells whose secretion of natural antibodies is suppressed by complexin 2.

一种新的 B1 B 细胞亚群，其天然抗体的分泌被复合蛋白 2 抑制。

• 发表时间: 2022
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• 通讯作者: 津田雅之

NF90-NF45はp53シグナル経路の抑制を介し肥満誘導代謝ストレスによる膵β細胞の代償性肥大を引き起こす

NF90-NF45 通过抑制 p53 信号通路诱导肥胖引起的代谢应激引起的胰腺 β 细胞代偿性肥大

• 发表时间: 2022
• 作者: Sylvia Lai;樋口琢磨;津田雅之;杉山憲康;森澤啓子;坂本修士
• 通讯作者: 坂本修士

17O-MRSによる慢性期脳性麻痺モデルマウスの脳内17O水の観測

17O-MRS对慢性脑瘫模型小鼠脑内17O水的观察

• 发表时间: 2022
• 作者: 津田正史,津田雅之,中山登;中岡渓;中岡茂
• 通讯作者: 中岡茂