Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose.
Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose.
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DOI：
10.1371/journal.pone.0002494
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发表时间：
2008-06-25
期刊：
影响因子：
3.7
通讯作者：
Sanberg PR
中科院分区：
文献类型：
--
作者：
Garbuzova-Davis S;Sanberg CD;Kuzmin-Nichols N;Willing AE;Gemma C;Bickford PC;Miller C;Rossi R;Sanberg PR
肌萎缩侧索硬化症（ALS）是一种以脊髓和大脑运动神经元变性为特征的多病因疾病。细胞疗法可能是治疗这种毁灭性疾病的一种有前途的新疗法。我们最近表明，单次低剂量（106个细胞）的单核人脐带血（MNC hUCB）细胞静脉注射给G93 A小鼠延迟症状进展和适度延长寿命。该临床前转化研究的目的是优化MNC hUCB细胞的剂量以延缓G93 A小鼠的疾病进展。将三种不同剂量的MNC hUCB细胞（10×106、25×106和50×106）静脉内给予症状前G93 A小鼠。对这些小鼠进行运动功能测试和各种测定以确定细胞效应。我们的研究结果表明，25×106个细胞的细胞剂量显著增加了小鼠20-25%的寿命，并延迟了15%的疾病进展。在这组小鼠中发现了减少脑和脊髓中促炎细胞因子的最有益效果。在接受25×106个细胞的小鼠血浆中发现了人Th 2细胞因子，尽管在50×106个细胞的小鼠中显示了普遍的人Th 1细胞因子。在接受25×106（主要）和10×106细胞的小鼠中，脾细胞对有丝分裂原（PHA）有高反应。仅在接受25×106个细胞的动物中发现外周血中淋巴细胞显著增加和中性粒细胞减少。在给予25×106个细胞的小鼠中，也观察到颈脊髓和腰脊髓中小胶质细胞密度稳定降低。这些结果表明，用适当剂量的MNC hUCB细胞治疗ALS可以通过这些细胞主动参与调节宿主免疫炎症系统应答来为运动神经元提供神经保护作用。
Amyotrophic Lateral Sclerosis (ALS) is a multicausal disease characterized by motor neuron degeneration in the spinal cord and brain. Cell therapy may be a promising new treatment for this devastating disorder. We recently showed that a single low dose (106 cells) of mononuclear human umbilical cord blood (MNC hUCB) cells administered intravenously to G93A mice delayed symptom progression and modestly prolonged lifespan. The aim of this pre-clinical translation study is to optimize the dose of MNC hUCB cells to retard disease progression in G93A mice. Three different doses of MNC hUCB cells, 10×106, 25×106 and 50×106, were administered intravenously into pre-symptomatic G93A mice. Motor function tests and various assays to determine cell effects were performed on these mice. Our results showed that a cell dose of 25×106 cells significantly increased lifespan of mice by 20–25% and delayed disease progression by 15%. The most beneficial effect on decreasing pro-inflammatory cytokines in the brain and spinal cord was found in this group of mice. Human Th2 cytokines were found in plasma of mice receiving 25×106 cells, although prevalent human Th1 cytokines were indicated in mice with 50×106 cells. High response of splenic cells to mitogen (PHA) was indicated in mice receiving 25×106 (mainly) and 10×106 cells. Significantly increased lymphocytes and decreased neutrophils in the peripheral blood were found only in animals receiving 25×106 cells. Stable reduction in microglia density in both cervical and lumbar spinal cords was also noted in mice administered with 25×106 cells. These results demonstrate that treatment for ALS with an appropriate dose of MNC hUCB cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response.
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影响因子：
9.9
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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发表时间：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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