Kohyama J, Abe H, Shimazaki T, Koizumi A, Nakashima K, Gojo S, Taga T, Okano H, Hata J, Umezawa A
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Differentiation. 2001 Oct;68(4-5):235-44. doi: 10.1046/j.1432-0436.2001.680411.x.
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.
骨髓基质细胞能够分化为脂肪生成、软骨生成、肌生成、骨生成和心肌生成谱系，所有这些都局限于中胚层来源。在本研究中，我们表明，外胚层起源的神经元可以通过特定诱导剂、纤连蛋白/鸟氨酸包被和神经球形成，从骨髓来源的基质细胞中产生。由骨髓基质产生的神经元形成神经突，表达神经元特异性标志物和基因，并开始作为功能成熟的神经元对去极化刺激作出反应。在基质细胞中，具有强大体内成骨活性的分离成熟成骨细胞可以有效地转化为功能性神经元。与能够改变基因表达模式的去甲基化剂5-氮杂胞苷相比，骨形态发生蛋白抑制剂Noggin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。
