首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice.
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Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice.

机译:来自骨髓的人干/祖细胞促进小鼠海马中内源性神经干细胞的神经发生。

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Stem/progenitor cells from bone marrow and other sources have been shown to repair injured tissues by differentiating into tissue-specific phenotypes, by secreting chemokines, and, in part, by cell fusion. Here we prepared the stem/progenitor cells from human bone marrow (MSCs) and implanted athem into the dentate gyrus of the hippocampus of immunodeficient mice. The implanted human MSCs markedly increased the proliferation of endogenous neural stem cells that expressed the stem cell marker Sox2. Labeling of the mice with BrdUrd demonstrated that, 7 days after implantation of the human MSCs, BrdUrd-labeled endogenous cells migrated throughout the dorsal hippocampus (positive for doublecortin) and expressed markers for astrocytes and for neural or oligodendrocyte progenitors. Subpopulations of BrdUrd-labeled cells exhibited short cytoplasmic processes immunoreactive for nerve growth factor and VEGF. By 30 days after implantation, the newly generated cells expressed markers for more mature neurons and astrocytes. Also, subpopulations of BrdUrd-labeled cells exhibited elaborate processes immunoreactive for ciliary neurotrophic factor, neurotrophin-4/5, nerve growth factor, or VEGF. Therefore, implantation of human MSCs stimulated proliferation, migration, and differentiation of the endogenous neural stem cells that survived as differentiated neural cells. The results provide a paradigm to explain recent observations in which MSCs or related stem/progenitor cells were found to produce improvements in disease models even though a limited number of the cells engrafted.
机译:骨髓和其他来源的干/祖细胞已显示出通过分化成组织特异性表型,分泌趋化因子以及部分通过细胞融合来修复受损组织。在这里,我们从人骨髓(MSCs)中制备了干/祖细胞,并将其植入了免疫缺陷小鼠海马的齿状回中。植入的人MSC显着增加了表达干细胞标记Sox2的内源性神经干细胞的增殖。用BrdUrd标记小鼠证明,在植入人MSC的7天后,BrdUrd标记的内源性细胞迁移到整个背侧海马(双皮质素呈阳性)并表达星形胶质细胞和神经或少突胶质祖细胞的标志物。 BrdUrd标记的细胞亚群显示出对神经生长因子和VEGF免疫反应的短细胞质过程。植入后30天,新生成的细胞表达了更多成熟神经元和星形胶质细胞的标志物。同样,BrdUrd标记的细胞亚群显示出对睫状神经营养因子,neurotrophin-4 / 5,神经生长因子或VEGF具有免疫反应性的精细过程。因此,人MSC的植入刺激了作为分化的神经细胞存活的内源性神经干细胞的增殖,迁移和分化。该结果为解释最近的观察提供了范例,在该观察中,即使移植了数量有限的细胞,也发现MSC或相关干/祖细胞在疾病模型中产生了改善。

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