Cord Blood Cells in ALS: Replacement of Protection?

ALS 中的脐带血细胞：替代保护？

• 批准号: 6789216
• 负责人: SVITLANA NICOLAI GARBUZOVA-DAVIS
• 金额: $ 14.44万
• 依托单位: SANERON CCEL THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789216
• 关键词: amyotrophic lateral sclerosis; behavior test; cell population study; cord blood; cryopreservation; cytoprotection; flow cytometry; genetically modified animals; hematopoietic stem cells; human tissue; inflammation; laboratory mouse; motor neurons; neuroimmunomodulation; neurotrophic factors; nonhuman therapy evaluation; stem cell transplantation

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.

描述（由申请人提供）：肌萎缩侧索硬化症（ALS）是一种影响脊髓、脑干和皮质中运动神经元的致死性退行性疾病。我们以前已经表明，将神经元细胞移植到脊髓中延迟了ALS的G93A小鼠模型中运动症状的发作，但是当ALS中存在广泛的神经变性时，围绕定向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潜能性，可能能够保护垂死的运动神经元，防止疾病进展。然而，这些影响背后的机制尚不清楚。我们假设来自脐带血的干细胞（hUCB）将通过调节免疫效应子而具有神经保护作用。本项目的目的是确定单核hUCB（MNC hUCB）细胞群是否可以作为移植细胞的新来源，以改善ALS的G93A小鼠模型的行为缺陷和延长寿命。在目的1中，我们将确定ALS小鼠中MNC hUCB移植与小鼠的运动功能和寿命之间的剂量反应关系。在目标2中，我们将确定移植的MNC hUCB细胞向变性区域的分布和迁移潜力，以及它们是否可以在体内采用免疫表型。在目的3中，我们将通过检查G93A小鼠中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、非侵入性的、容易被ALS患者接受的治疗方法提供基础。

项目成果

Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose.

• DOI: 10.1371/journal.pone.0002494
• 发表时间: 2008-06-25
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Garbuzova-Davis S;Sanberg CD;Kuzmin-Nichols N;Willing AE;Gemma C;Bickford PC;Miller C;Rossi R;Sanberg PR
• 通讯作者: Sanberg PR