Neurogenic potential of progenitors derived from human circulating CD14+ monocytes
Neurogenic potential of progenitors derived from human circulating CD14+ monocytes
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DOI：
10.1111/j.1440-1711.2006.01424.x
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
Kuwana, M
中科院分区：
文献类型：
--
作者：
Kodama, H;Inoue, T;Kuwana, M
我们先前报道了一种来源于人循环CD 14（+）单核细胞的原始细胞组分，称为单核细胞衍生的多能细胞（MOMC），其可沿沿着间充质谱系分化，包括骨、软骨、脂肪、骨骼肌和心肌。在这项研究中，我们研究了MOMC是否可以分化为神经元谱系。MOMC荧光标记和共培养与原代培养的大鼠神经元长达4周。随着时间的推移，在人类MOMC神经元特异性标志物的蛋白质和基因表达进行了评估，使用免疫组化，原位杂交和逆转录，然后PCR。与大鼠神经元共培养后不久，几乎所有的MOMC表达早期神经外胚层标记物，Mash 1，Neurogenin 2和NeuroD，以及巢蛋白，在神经发生中表达的中间丝。共培养14天后，MOMC的亚群显示出多极形态，具有细长的神经突，并表达成熟的神经元特异性标记物，包括神经丝、微管相关蛋白2型、β 3-微管蛋白、NeuN和Hu。单核细胞转分化为神经外胚层谱系的同时表达的前神经标记物和CD 45/CD 14的早期分化过程。共培养的MOMC保持其增殖能力至少16天。最后，在无细胞接触的情况下，观察MOMC与神经元共同培养时的神经元分化。MOMC分化为中胚层和神经外胚层谱系的能力表明循环中的CD 14（+）单核细胞比以前认为的更具多能性。
We previously reported a primitive cell fraction derived from human circulating CD14(+) monocytes, named monocyte-derived multipotential cells (MOMC), that can differentiate along mesenchymal lineages, including bone, cartilage, fat, skeletal muscle and cardiac muscle. In this study, we investigated whether MOMC can differentiate into the neuronal lineage. MOMC were fluorescently labelled and cocultivated with a primary culture of rat neurons for up to 4 weeks. The protein and gene expressions of neuron-specific markers in the human MOMC were evaluated over time using immunohistochemistry, in situ hybridization and reverse transcription followed by PCR. Shortly after cocultivation with rat neurons, nearly all the MOMC expressed early neuroectodermal markers, Mash1, Neurogenin2 and NeuroD, together with nestin, an intermediate filament expressed in neurogenesis. After 14 days of coculture, a subpopulation of MOMC displayed a multipolar morphology with elongated neurites and expressed mature neuron-specific markers, including neurofilament, microtubule-associated protein type 2, beta 3-tubulin, NeuN and Hu. Transdifferentiation of monocytes into the neuroectodermal lineage was shown by the simultaneous expression of proneural markers and CD45/CD14 early in the differentiation process. The cocultivated MOMC retained their proliferative capacity for at least 16 days. Finally, the neuronal differentiation of MOMC was observed when they were cultured with neurons without cell-to-cell contact. The capacity of MOMC to differentiate into both mesodermal and neuroectodermal lineages suggests that circulating CD14(+) monocytes are more multipotential than previously thought.