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The reset and transdifferentiation of bone marrow stromal cells and developmental research for organ regeneration

骨髓基质细胞的重置、转分化及器官再生的发育研究

基本信息

批准号：
15590166
负责人：
DEZAWA Mari
金额：
$ 2.37万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

Bone marrow stromal cells (MSCs) have the capability under specific conditions to differentiate into other cell types. In this study, we demonstrate a highly efficient and specific induction of cells with neuronal, Schwann cells and skeletal muscle characteristics.Neurons : MSCs were transfected with Notch intracellular domain(NICD) followed by cytokine treament. (bFGF+CNTF+forskolin). Induced neuronal cells expression neuronal markers, and showed voltage-gated fast sodium and action potentials. Glial markers could not be detected. Further treatment of the induced neuronal cells with GDNF increased the proportion of tyrosine hydroxylase (TH)-positive cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior, following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson's disease.Schwann cells : Cells were treated with beta-mercaptoethanol and retinoic acid, followed by treatment with cytokines of bFGF, FSK, PD … More GF and neuregulin. MSCs changed their morphology after treatment with expression of Schwann cell markers of p75, GFAP, S-100 and P0. Transplantation of induced cells improved the function of spinal cord contusion injury model rats.Skeletal muscle cells : MSCs were treated with cytokines (FSK+bFGF+PGDF+neuregulin) followed by NICD transfection. Induced cells expressed MyoD, Myogenin and other skeletal muscle markers and Pax7, c-MetR satellite cell markers, and formed multinuclear skeletal muscle cells. After intravenous transplantation of induced cell, muscle regeneration and integration of induced cells could be observed in mdx-mice (muscle dystrophy model mice).MSCs have a great potential as therapeutic agents against neurological diseases since they can be readily obtained through a well-established clinical procedure and are easy to isolate and expand for autotransplantation with no risk of rejection. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach. Less

骨髓基质细胞（MSCs）在特定条件下具有分化为其他细胞类型的能力。在本研究中，我们证明了一种高效和特异性的诱导细胞具有神经元，雪旺细胞和骨骼肌的特性。神经元：MSC转染Notch细胞内结构域（NICD），然后用细胞因子处理。(bFGF+CNTF+毛喉素）。诱导的神经元细胞表达神经元标记物，并显示电压门控快钠和动作电位。未检测到神经胶质标志物。进一步用GDNF处理诱导的神经元细胞增加酪氨酸羟化酶（TH）阳性细胞的比例。将这些GDNF处理的细胞移植到帕金森病的6-羟基多巴胺大鼠模型的纹状体内后，显示出阿扑吗啡诱导的旋转行为的改善。 ...更多信息 GF和神经调节蛋白。在表达雪旺细胞标志物p75、GFAP、S-100和P0的处理后，MSC改变其形态。骨骼肌细胞：细胞因子（FSK+bFGF+PGDF+neuregulin）处理MSCs后，NICD转染。诱导细胞表达MyoD、Myogenin等骨骼肌标志物和Pax 7、c-MetR卫星细胞标志物，形成多核骨骼肌细胞。静脉内移植诱导细胞后，在mdx小鼠（肌肉营养不良模型小鼠）中可以观察到肌肉再生和诱导细胞的整合。MSC作为神经系统疾病的治疗剂具有很大的潜力，因为它们可以通过完善的临床程序容易地获得，并且易于分离和扩增用于自体移植，没有排斥反应的风险。这项研究表明，一个群体的神经元细胞可以特异性地产生从骨髓间充质干细胞和诱导细胞可能允许神经重建的方法。少

项目成果

期刊论文数量（72）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ishikawa H, Takano M, Matsumoto N, Sawada H, Ide C, Mimura O, Dezawa M: "The effect of GDNF gene transfer into axotomized retinal ganglion cells using in vivo electroporation with contact type electrode Gene"Gene Therapy. (in press).

Ishikawa H、Takano M、Matsumoto N、Sawada H、Ide C、Mimura O、Dezawa M：“使用接触型电极体内电穿孔将 GDNF 基因转移到轴突视网膜神经节细胞中的效果”基因治疗。

DOI：
发表时间：
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影响因子：
0
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Implantation of neural stem cells via cerebrospinal fluid into the injured root

通过脑脊液将神经干细胞植入受伤的根部

DOI：
发表时间：
2004
期刊：
Neuroreport. 15(8)
影响因子：
0
作者：
Ohta M;Suzuki Y;Noda T;Kataoka K;Chou H;Ishikawa N;Kitada M;Matsumoto N;Dezawa M;Suzuki S;Ide C
通讯作者：
Ide C

Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve