Cord Blood Cells in ALS: Replacement of Protection?

描述（由申请人提供）：肌萎缩性侧索硬化症（ALS）是一种影响脊髓、脑干和皮层运动神经元的致命退行性疾病。我们之前的研究表明，在ALS的G93A小鼠模型中，将神经元细胞移植到脊髓中可以延缓运动症状的发生，但是当ALS存在广泛的神经变性时，围绕一个固定的神经元细胞或细胞系开发潜在的治疗策略是不合适的。干细胞具有公认的迁移能力和多能性，可能能够保护垂死的运动神经元并防止疾病进展。然而，这些影响背后的机制尚不清楚。我们假设脐带血干细胞（huhb）通过调节免疫效应器具有神经保护作用。本项目的目的是确定单核hub （MNC hub）细胞群是否可以作为一种新的移植细胞来源，改善ALS G93A小鼠模型的行为缺陷和延长寿命。在Aim 1中，我们将确定ALS小鼠MNC hub移植与小鼠运动功能和寿命之间的剂量反应关系。在目的2中，我们将确定移植的MNC hub细胞到变性区域的分布和迁移潜力，以及它们是否可能在体内采用免疫表型。在Aim 3中，我们将通过检测G93A小鼠的细胞因子表达来确定移植细胞对宿主免疫炎症反应的影响。这项研究的结果可能为开发一种新的、无创的、ALS患者容易获得的治疗方法提供基础。

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease affecting motor neurons in the spinal cord, brainstem and cortex. We have previously shown that transplanting neuronal cells into the spinal cord delays the onset of motor symptoms in the G93A mouse model of ALS, but developing a potential treatment strategy around a committed neuronal cell or cell-line is not appropriate when there is widespread neurodegeneration as in ALS. Stem cells with their putative migratory abilities and multipotentiality may be able to protect dying motor neurons and prevent disease progression. However, the mechanism behind these effects is unknown. We hypothesize that stem cells from umbilical cord blood (hUCB) will have a neuroprotective effect through modulation of immune effectors. The purpose of this project is to determine whether the mononuclear hUCB (MNC hUCB) cell population can serve as a novel source of transplant cells to ameliorate behavioral deficits and extend lifespan in the G93A mouse model of ALS. In Aim 1 we will determine a dose response relationship between MNC hUCB transplantation in the ALS mouse and motor function and lifespan of the mouse. In Aim 2 we will determine the distribution and migration potential of the transplanted MNC hUCB cells to areas of degeneration and if they may adopt immune phenotypes in vivo. In Aim 3 we will determine the effect of the transplanted cells on host immune inflammatory response by examining cytokine expression in G93A mice. The results of this study may provide the basis for developing a novel, non-invasive therapy, easily accessed by ALS patients.