Brain from bone: Efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent
Brain from bone: Efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent
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DOI：
10.1046/j.1432-0436.2001.680411.x
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发表时间：
2001-10-01
期刊：
影响因子：
2.9
通讯作者：
Umezawa, A
中科院分区：
文献类型：
--
作者：
Kohyama, J;Abe, H;Umezawa, A
骨髓基质细胞能够分化成脂肪形成、软骨形成、肌形成、骨形成和心肌形成谱系，所有这些谱系都仅限于中胚层来源。在这项研究中，我们表明，外胚层来源的神经元可以通过特定诱导剂、纤连蛋白/鸟氨酸涂层和神经球形成从骨髓源性基质细胞产生。骨髓基质产生的神经元形成神经突，表达神经元特异性标记物和基因，并开始作为功能性成熟神经元对去极化刺激做出反应。在基质细胞中，分离出的具有强体内成骨活性的成熟成骨细胞可以有效地转化为功能性神经元。与5-氮杂胞苷（一种能够改变基因表达模式的去甲基化剂）相比，Noggin（一种骨形态发生蛋白抑制剂）增强了这种转分化或元分化。因此，骨髓基质是神经细胞移植的潜在细胞来源。
Bone marrow stromal cells are able to differentiate into adipogenic, chondrogenic, myogenic, osteogenic, and cardiomyogenic lineages, all of which are limited to a mesoderm-derived origin. In this study, we showed that neurons, which are of an ectoderm-origin, could be generated from marrow-derived stromal cells by specific inducers, fibronectin/ornithine coating, and neurosphere formation. The neurons generated from marrow stroma formed neurites, expressed neuron-specific markers and genes, and started to respond to depolarizing stimuli as functional mature neurons, Among stromal cells, isolated mature osteoblasts which had strong in vivo osteogenic activity could be efficiently converted into functional neurons. This transdifferentiation or meta-differentiation was enhanced by Noggin, an inhibitor of bone morphogenetic proteins, in comparison with 5-azacytidine, a demethylating agent capable of altering the gene expression pattern. Marrow stroma is therefore a potential source of cells for neural cell transplantation.