Autologous transplantation of neural stem cells in neonatalhypoxic ischemic brain injury in rats

自体神经干细胞移植治疗新生大鼠缺氧缺血性脑损伤

• 批准号: 22591204
• 负责人: IWAI Masanori
• 金额: $ 2.83万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591204/
• 关键词: 脳梗塞巣; 新生児低酸素性虚血性脳症; 神経幹細胞; 自己移植; Neurosphere 法; 内在性神経幹細胞; 新生児; 低酸素性虚血性脳症; 神経幹細胞賦活; 再生医療; Neurosphere法; 脳室内投与; EGF; b-FGF

In this study, neural stem/neural progenitor cells with strongmitotic ability were obtained from the ischemic brain lesion at 3 says after neonatalhypoxic ischemic insult in rats. However, aspiration of ischemic tissue from neonatalbrain led to expand of ischemic lesions on MRI image and worsen of motor function test.Therefore, we changed the therapeutic method of this study from autologoustransplantation to enhancement intrinsic neural stem/ neural progenitor cells in thesubventricular zone (SVZ) and ischemic lesions with intraventricular injection of EGFand FGF which were usually used on neurosphere culture method. This method led to increasebromodeoxyuridine (BrdU) labeled cells in the SVZ, lower edge of corpus callosum andaround of ischemic lesion. Histological investigation of brain tissue at 7days afterhypoxia ischemia, almost all BrdU labeled cells were double labeled with neural progenitormaker DCX, astrocyte maker GFAP and oligodendrocyte progenitor maker O4, respectively.Therefore, BrdU labeled cells were seemed to still undifferentiated stage in thisanalysis.

本研究从大鼠脑缺血缺氧损伤后3天的脑组织中分离获得了具有较强有丝分裂能力的神经干/神经前体细胞。然而，由于脑缺血组织的抽吸导致MRI图像上缺血病灶扩大和运动功能测试恶化，因此，我们改变了本研究的治疗方法，从自体移植到脑室内注射通常用于神经球培养方法的EGF和FGF，以增强脑室下区（SVZ）和缺血病灶内的内源性神经干/神经祖细胞。这种方法使SVZ、胼胝体下缘及缺血灶周围的BrdU标记细胞增多。缺氧缺血后7 d脑组织病理学观察，几乎所有BrdU标记细胞均分别被神经祖细胞标记物DCX、星形胶质细胞标记物GFAP和少突胶质细胞标记物O 4双重标记，因此，在本分析中，BrdU标记细胞仍处于未分化阶段。

项目成果

Neural stem cells with high mitotic activity exist in the injured area of neonatal brain after hypoxic ischemic insult

缺氧缺血性损伤后新生儿脑损伤区存在高有丝分裂活性的神经干细胞

• 发表时间: 2013
• 作者: M Ichinose;Y Kamei;S Imada;T Seyama;T Iriyama;S Kozuma;Y Taketani;H Asou;Masanori Iwai
• 通讯作者: Masanori Iwai

Isolation and characterizationof neural stem/progenitor cells frominfarct area in neonatal rat brain

新生大鼠脑梗死区神经干/祖细胞的分离和表征

• 发表时间: 2012
• 作者: Jun Kido;Masanori Iwai;ShirouMatsumoto;Hiroko Tajiri;KimitoshiNakamura;Hiroshi Mitsubuchi;FumioEndo
• 通讯作者: FumioEndo