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

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。在这项研究中，我们展示了一种高效和特异的诱导具有神经元、雪旺细胞和骨骼肌特征的细胞。神经元：将Notch胞内域(NICD)转染间充质干细胞，然后进行细胞因子处理。(碱性成纤维细胞生长因子+CNTF+Forsklin)。诱导神经细胞表达神经元标志物，并显示电压门控性快钠和动作电位。未检测到神经胶质标记物。进一步用GDNF处理诱导的神经细胞，可增加酪氨酸羟化酶(TH)阳性细胞的比例。在6-羟基多巴胺帕金森病大鼠模型中，移植这些经神经营养因子处理的细胞在阿朴吗啡诱导的旋转行为中表现出改善。雪旺细胞：细胞用β-巯基乙醇和维甲酸处理，然后用碱性成纤维细胞生长因子，fsk，PD，…处理更多的生长因子和神经调节蛋白。雪旺细胞标志物p75、胶质纤维酸性蛋白、S-100和P0的表达改变了MSCs的形态。诱导细胞移植可改善脊髓挫伤模型大鼠的功能。骨骼肌细胞：骨髓间充质干细胞用细胞因子(FSK+bFGF+PGDF+neuRegin)处理后，NICD转染组。诱导细胞表达MyoD、Mygenin等骨骼肌标记物和Pax7、c-metr卫星细胞标记物，形成多核骨骼肌细胞。在mdx小鼠(肌营养不良模型小鼠)静脉移植诱导细胞后，可以观察到诱导细胞的肌肉再生和整合。由于MSCs可以通过成熟的临床程序容易获得，并且易于分离和扩增，用于自体移植，没有排斥反应的风险，因此在治疗神经系统疾病方面具有巨大的潜力。这项研究表明，MSCs可以特异性地产生一组神经细胞，诱导的细胞可能允许一种神经重建方法。较少

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