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：
IDE Chizuka
金额：
$ 10.69万
依托单位：
Kyoto University Graduate School of Medicine
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

根据早期实验，我们认识到，在临床上应用神经干细胞存在很大的障碍：这些是关于使用胎儿和不可避免的过敏性移植的道德问题。另一方面，骨髓基质细胞（BMSC）在临床应用中具有很大的优势。在实验中，通过大鼠的第4次通风将BMSC注入脑脊液（CSF）。许多注射的BMSC附着在脊髓表面，其中一些进一步入侵了病变。基于BBB量表，细胞移植大鼠的运动显示14 15和11点，而对照组分别为10和8点，分别在轻度和强烈的脊髓挤压中。脊髓腔的大小为大约。细胞移植大鼠中的1/2比对照小。观察到星形胶质细胞的增殖较少，并且在细胞移植大鼠中保留了更多的神经成分。注射细胞消失了……在注射后4-5周内，从脊髓中消失了。这意味着注射BMSC的注射不是通过将某些营养因子释放到CSF中来执行其效果。体外实验也支持了这一假设。 BMSC的作用不是干细胞，而是源自成年动物的普通体细胞。据认为，BMSC抑制退化过程，同时促进了变性早期受伤细胞的存活。我们通过通过腰椎注射自体BMSC来证实BMSC注入猴子中CSF的安全性。我们提供了一项完整的临床应用方案，Kansai大学的道德委员会批准了通过BMSC移植到2005年7月1日^<ST> 2005年的脊髓损伤患者向脊髓疗法的患者移植的。缺血性脑损伤，并澄清说，培养的脉络丛细胞的注射对脑组织从缺血性损伤中恢复有很大影响。这一发现可能为缺血性脑损伤的治疗打开了新的视野。较少的

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：
藍野大学紀要 (印刷中)
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：
細胞 37
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：
Aino Journal (in press)
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：
Encyclopedic Reference in Neuroscience (in press)
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。