Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice
Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice
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DOI：
10.1073/pnas.0508945102
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发表时间：
2005-12-13
影响因子：
11.1
通讯作者：
Prockop, DJ
中科院分区：
文献类型：
--
作者：
Munoz, JR;Stoutenger, BR;Prockop, DJ
来自骨髓和其他来源的干/祖细胞已显示通过分化成组织特异性表型、通过分泌趋化因子以及部分通过细胞融合来修复受损组织。本研究从人骨髓中提取干/祖细胞，并将其植入免疫缺陷小鼠海马齿状回。植入的人MSC显著增加了表达干细胞标志物Sox 2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后7天，BrdUrd标记的内源性细胞在整个背侧海马中迁移（双皮质素阳性），并表达星形胶质细胞和神经或少突胶质细胞祖细胞的标记物。BrdUrd标记的细胞亚群表现出神经生长因子和VEGF免疫反应性的短胞质突起。植入后30天，新产生的细胞表达了更成熟的神经元和星形胶质细胞的标记物。此外，BrdUrd标记的细胞亚群表现出复杂的睫状神经营养因子，神经营养因子-4/5，神经生长因子，或VEGF的免疫反应过程。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。这些结果提供了一个范例来解释最近的观察结果，其中发现MSC或相关干/祖细胞在疾病模型中产生改善，即使移植的细胞数量有限。
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 them 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.