IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells.

IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells.
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DOI:
10.1186/1471-2202-15-91
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发表时间:
2014-07-22
期刊:
影响因子:
2.4
通讯作者:
Jaafar H
Jaafar H
中科院分区:
医学4区
文献类型:
--
作者:
Huat TJ;Khan AA;Pati S;Mustafa Z;Abdullah JM;Jaafar H

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近年来,间充质干细胞(MSCs)的可塑性及其向神经细胞分化的潜能受到越来越多的关注。为了阐明不同生长因子在MSC分化成神经谱系中的作用和影响,我们使用不同的生长因子组合将MSC分化成神经谱系。基于以前的研究胰岛素样生长因子1(IGF-1)在神经干细胞分离在实验室中的作用,我们假设,IGF-1可以促进增殖和减少神经祖细胞(NPC)在分化为NCPs的过程中。我们在四种不同的生长因子组合下诱导MSC分化:(A)EGF + bFGF,(B)EGF + bFGF + IGF-1,(C)EGF + bFGF + LIF,(D)EGF + bFGF + BDNF,和(E)无生长因子,作为阴性对照。通过对巢蛋白的免疫荧光染色来表征所形成的神经球,并且通过流式细胞术来测量表达。MTS和Annexin V测定也分别在三个不同的时间间隔(24小时,3天和5天)研究了细胞增殖和凋亡。四组中形成的神经球然后终末分化为神经元和胶质细胞。四种衍生的NPC显示出比阴性对照所示的显着更高的巢蛋白表达。在用生长因子处理的组中,用IGF-1处理的NPC显示巢蛋白的最高表达。此外,使用IGF-1衍生的NPC在处理组中表现出最高的细胞增殖和细胞存活。与其他处理组相比,来自IGF-1处理的NPC在终末分化为神经元和神经胶质细胞后的产量也更高。我们的结果表明,IGF-1通过促进NPC的增殖和减少凋亡,在MSC向神经元谱系分化中发挥关键作用。从长远来看,这些信息将有利于改善神经退行性疾病的细胞治疗和无细胞治疗。
There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs. We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells. The four derived NPCs showed a significantly higher expression of nestin than was shown by the negative control. Among the groups treated with growth factors, NPCs treated with IGF-1 showed the highest expression of nestin. Furthermore, NPCs derived using IGF-1 exhibited the highest cell proliferation and cell survival among the treated groups. The NPCs derived from IGF-1 treatment also resulted in a better yield after the terminal differentiation into neurons and glial cells than that of the other treated groups. Our results suggested that IGF-1 has a crucial role in the differentiation of MSCs into neuronal lineage by enhancing the proliferation and reducing the apoptosis in the NPCs. This information will be beneficial in the long run for improving both cell-based and cell-free therapy for neurodegenerative diseases.
DOI: 10.1634/stemcells.2004-0149
发表时间: 2005-03-01
期刊: STEM CELLS
影响因子: 5.2
作者:
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DOI: 10.1016/j.brainres.2008.06.087
发表时间: 2008-09-10
期刊: BRAIN RESEARCH
影响因子: 2.9
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发表时间: 2005-11-01
影响因子: 2.6
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