Establishment of adult rat-derived stem cells, and histological/functional reconstruction of spinal cord by auto- and allo-grafting of those stem cells

建立成年大鼠来源的干细胞,并通过这些干细胞的自体和同种异体移植进行脊髓的组织学/功能重建

基本信息

  • 批准号:
    15300114
  • 负责人:
  • 金额:
    $ 10.69万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

Based on the early experiments, we recognized that there are big barriers for neural stem cells to be clinically applied : those are ethical problems concerning the use of fetus and inevitable allergenic transplantation. On the other hand, bone marrow stromal cells (BMSCs) have great advantages in being autogenic for clinical application. In experiments, BMSCs were injected into the cerebrospinal fluid (CSF) through the 4^th ventricle of the rat. Many injected BMSCs were attached to the spinal cord surface, and some of them further invaded the lesion. Based on the BBB scale, cell-graft rats showed 14 15 and 11 points in locomotion, while the controls were 10 and 8 points, in the mild and strong spinal cord crush, respectively. The size of spinal cord cavity was ca. 1/2 smaller in the cell-graft rats than the controls. Less proliferation of astrocytes was observed, and a larger amount of neural components was preserved in the cell-graft rats than in the controls.Injected cells disappear … More ed from the spinal cord within 4-5 weeks after injection. This implies that injected BMSCs exerted their effects not by being integrated into the host tissue, but by releasing some trophic factors into the CSF. The in vitro experiments also supported this hypothesis. BMSCs function not as stem cells, but as ordinary somatic cells derived from adult animals. It is considered that BMSCs suppress the degenerative processes, and at the same time promote the survival, of injured cells at the early stage of degeneration. We confirmed the safety of BMSC injection into the CSF in the monkey by injecting autogenic BMSCs through lumbar puncture. We provided a complete protocol for clinical application, and the Ethic Committee of Kansai University approved this cell transplantation to patients with spinal cord therapy by BMSC transplantation to patients with spinal cord injury on July 1^<st> 2005. We are now ready for the BMSC transplantation therapy to patients matched to the protocol.In parallel with this study, we also examined the effects of choroid plexus ependymal (epithelial) cells to the ischemic brain injury, and clarified that the injection of cultured choroid plexus ependymal cells have a great effect on the recovery of brain tissue from ischemic damages. This finding might open a new horizon for the therapy of ischemic brain injury. Less
基于早期的实验,我们认识到神经干细胞的临床应用存在很大的障碍:胎儿使用的伦理问题和不可避免的过敏性移植。另一方面,骨髓基质细胞(BMSCs)有很大的障碍。在临床应用中,BMSCs通过大鼠第四脑室注射到脑脊液(CSF)中,许多注射的BMSCs附着在脊髓上。根据 BBB 评分,细胞移植大鼠在轻度和强烈脊髓挤压中分别显示 14、15 和 11 分,而对照组分别为 10 和 8 分。细胞移植大鼠的脊髓腔大小比对照组小约 1/2,观察到星形胶质细胞的增殖较少,并且细胞移植大鼠中保留了更多的神经成分。注射后 4-5 周内,注射的细胞从脊髓中消失,这意味着注射的 BMSC 不是通过整合到宿主组织中来发挥作用,而是通过将一些营养因子释放到脑脊液中。也支持这一假设。BMSC 的功能不是作为干细胞,而是作为源自成年动物的普通体细胞。BMSC 可以抑制早期受损细胞的退化过程,同时促进其存活。我们通过腰椎穿刺注射自体BMSCs证实了BMSCs注射到猴子脑脊液中的安全性,我们提供了完整的临床应用方案,并且关西大学伦理委员会批准了这种细胞移植到脊髓治疗的患者。 2005 年 7 月 1 日,我们通过 BMSC 移植对脊髓损伤患者进行了治疗。我们现在已准备好按照方案对患者进行 BMSC 移植治疗。与这项研究同时,我们还检查了研究人员研究了脉络丛室管膜(上皮)细胞对缺血性脑损伤的影响,并阐明了注射培养的脉络丛室管膜细胞对缺血性脑组织的恢复有很大作用,这一发现可能为脑组织的缺血性损伤的恢复开辟新的视野。缺血性脑损伤的治疗较少。

项目成果

期刊论文数量(131)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
精髄再生研究の歩み
精华再生研究史
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kawai R.;Sunada H.;Horikoshi T.;Sakakibara M.;井出千束
  • 通讯作者:
    井出千束
脳脊髄液経由細胞移植法による脊髄損傷治療
脑脊液细胞移植治疗脊髓损伤
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    太田正佳;鈴木義久;井出千束
  • 通讯作者:
    井出千束
Concepts of cell transplantation for spinal cord injury - a short overview -
脊髓损伤细胞移植的概念 - 简短概述 -
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kato H;Tamamizu-Kato S;Shibasaki F.;Ide C.
  • 通讯作者:
    Ide C.
The role of basal lamina in nerve regeneration.
基底层在神经再生中的作用。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Li N;Nakamura K;Jiang Y;Tsurui H;Matsuoka S;Abe M;Ohtsuji M;Nishimura H;Kato K;Kawai T;Atsumi T;Koike T;Shirai T;Ueno H;Hirose S.;Ide C.
  • 通讯作者:
    Ide C.
Increase in bFGF-responsive neural progenitor population forllowing contusion injury of the adult rodent spinal cord.
成年啮齿动物脊髓挫伤后 bFGF 反应性神经祖细胞群增加。
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IDE Chizuka其他文献

IDE Chizuka的其他文献

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{{ truncateString('IDE Chizuka', 18)}}的其他基金

Mechanisms of spinal cord regeneration by transplantation of matured animal-derived somatic stem cells
成熟动物源性成体干细胞移植脊髓再生机制
  • 批准号:
    23300125
  • 财政年份:
    2011
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Cell transplantation for the treatment of spinal cord injury in rats-morphological study and search for humoral effective factors-
细胞移植治疗大鼠脊髓损伤-形态学研究及体液有效因子的寻找-
  • 批准号:
    20300122
  • 财政年份:
    2008
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Promotion of brain-and spinal-cord regeneration by transplantation of somatic cells(bone marrow stromal cells and choroid plexus ependymal cells)-mechanisms of rescuing injured neural cells, and perspectives for clinical applications-
体细胞(骨髓基质细胞、脉络丛室管膜细胞)移植促进脑脊髓再生-拯救受损神经细胞的机制及临床应用前景-
  • 批准号:
    17300110
  • 财政年份:
    2005
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Facilitation of central nerve regeneration by choroid plexus ependymal cells
脉络丛室管膜细胞促进中枢神经再生
  • 批准号:
    12480226
  • 财政年份:
    2000
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of artificial tubes to be used for repairing a large peripheral nerve gap
开发用于修复大周围神经间隙的人工管
  • 批准号:
    11559010
  • 财政年份:
    1999
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Study on the condition for central nerve regeneration-grafting of ependymal cells and cell proliferation by neuregulin-
神经调节素促进中枢神经再生-室管膜细胞移植及细胞增殖条件的研究
  • 批准号:
    10470005
  • 财政年份:
    1998
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Axon-Schwann cell relationship in nerve regeneration and the mechanisms for the promotion of nerve
神经再生中轴突-雪旺细胞的关系及促进神经的机制
  • 批准号:
    08457004
  • 财政年份:
    1996
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Expression of vesicle-associated proteins during the course of differentiation of growth cones into synaptic terminals in nerve regeneration (synaptophysin, synaptotagmin, protein kinase C,etc)
神经再生过程中生长锥分化为突触末梢过程中囊泡相关蛋白的表达(突触素、突触结合蛋白、蛋白激酶C等)
  • 批准号:
    06454142
  • 财政年份:
    1994
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Mechanisms of regenerating spout formation and growth in the peripheral nerves as studied by confocal laser scanning and immunoelectron microscopy
通过共焦激光扫描和免疫电子显微镜研究周围神经再生喷口形成和生长的机制
  • 批准号:
    04454126
  • 财政年份:
    1992
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
MODEL OF NERVE FIBER REGENERATION IN CNS BY EXCIMER LASER
准分子激光中枢神经系统神经纤维再生模型
  • 批准号:
    02557002
  • 财政年份:
    1990
  • 资助金额:
    $ 10.69万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)

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KDM4B 对口面部骨稳态和衰老的表观遗传调控
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