Autologous Bone Marrow Stromal Cell Transplantation for Stroke: Steps to Standardize the Clinical Protocols

自体骨髓基质细胞移植治疗中风：标准化临床方案的步骤

• 批准号: 23390342
• 负责人: SHICHINOHE Hideo
• 金额: $ 10.82万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390342/
• 关键词: 移植・再生医療; 脳神経外科; 骨髄間質細胞; 脳梗塞; 中枢神経再生; PET; MRI; スキャフォールド; 自家移植; Platelet lysate; G-CSF

Human bone marrow stromal cells (BMSCs) were cultured with human platelet lysate (hPL) instead of fetal calf serum (FCS). Their production of growth factors was quantified with ELISA. The BMSCs were labeled with superparamagnetic iron oxide (SPIO). Rat permanent focal ischemia models were made and BMSCs were injected into the ipsilateral striatum 7 days post-insult. There was no difference in cell proliferation between the BMSCs cultured with hPL and FCS. The BMSC-hPL produced not less amount of BDNF, HGF, NGF, PDGF-BB and TGF-beta1. Rotarod test showed that the motor function deteriorated after ischemia and BMSC transplantation enhanced the recovery. MRI demonstrated that the SPIO-BMSCs migrated towards the lesion. 18F-FDG PET showed that the recovery of glucose utilization was promoted. The hPL may be valuable and safe in expanding BMSCs. The application of bio-imaging techniques are also valuable for BMSC transplantation against stroke.

以人血小板裂解液（hPL）代替胎牛血清（FCS）培养人骨髓基质细胞（BMSCs）。用ELISA定量其生长因子的产生。用超顺磁性氧化铁（SPIO）标记骨髓基质细胞。制作大鼠永久性局灶性脑缺血模型，损伤后7天将BMSCs注入同侧纹状体。hPL与FCS共同培养的BMSCs的细胞增殖能力无明显差异。BMSC-hPL产生不少于BDNF、HGF、NGF、PDGF-BB和TGF-β 1的量。转棒试验显示缺血后运动功能恶化，骨髓间充质干细胞移植可促进缺血后运动功能的恢复。 MRI显示SPIO-BMSCs向病变方向迁移。18F-FDG PET显示葡萄糖利用率的恢复得到促进。hPL扩增BMSCs是安全可行的。生物成像技术的应用对于BMSC移植治疗中风也有价值。

项目成果

Steps to the Clinical Testing of Cell Transplantation for Stroke - Bone Marrow Stromal Cell Culture with Animal Protein-free Medium and Bio-imaging Using Clinical 3.0-Tesla MRI

中风细胞移植的临床测试步骤 - 使用无动物蛋白培养基的骨髓基质细胞培养和使用临床 3.0 特斯拉 MRI 的生物成像

• 发表时间: 2012
• 作者: Shichinohe H;et al
• 通讯作者: et al

骨髄間質細胞をもちいた再生医療のトランスレーショナルリサーチ - xeno-freeな細胞培養と定位移植後のMRI細胞追跡

骨髓基质细胞再生医学转化研究——立体定位移植后的无异源细胞培养和MRI细胞追踪

• 发表时间: 2012
• 作者: Ogura F;Wakao S;Kuroda Y;Tsuchiyama K;Bagheri M;Heneidi S;Chazenbalk G;Aiba S;Dezawa M;七戸秀夫
• 通讯作者: 七戸秀夫

I-Iomazenil Single Photon Emission Computed Tomography Visualizes Recovery of Neuronal Integrity by Bone Marrow Stromal Cell Therapy in Rat Infarct Brain

I-Iomazenil 单光子发射计算机断层扫描显示大鼠梗塞脑中骨髓基质细胞治疗神经元完整性的恢复

• 发表时间: 2013
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Saito H;Magota K;Zhao S;Kubo N;Kuge Y;Shichinohe H;Houkin K;Tamaki N;Kuroda S
• 通讯作者: Kuroda S

Neuroprotective Effects of Cilostazol through the Multi-mechanisms in Mice Permanent Focal Ischemia

西洛他唑通过多种机制对小鼠永久性局灶性缺血的神经保护作用

• 发表时间: 2014
• 作者: Shichinohe H;et al
• 通讯作者: et al

バイオイメージングを駆使した脳梗塞に対する再生医療

利用生物成像治疗脑梗塞的再生医学

• 发表时间: 2013
• 作者: 七戸秀夫;寳金清博;黒田 敏
• 通讯作者: 黒田 敏