Transplanted bone marrow generates new neurons in human brains
Transplanted bone marrow generates new neurons in human brains
复制标题
DOI：
10.1073/pnas.0336479100
复制
发表时间：
2003-02-04
影响因子：
11.1
通讯作者：
Crain, B
中科院分区：
文献类型：
--
作者：
Mezey, É;Key, S;Crain, B
成体骨髓干细胞在啮齿类动物中似乎分化成肌肉、皮肤、肝脏、肺和神经元细胞，并且已显示在人类中再生心肌、肝细胞、皮肤和胃肠道上皮。因为我们之前已经证明移植的骨髓细胞可以进入小鼠的大脑并在那里分化为神经元，所以我们决定检查接受男性骨髓移植的女性死后的大脑样本。患者的基础疾病是淋巴细胞白血病和免疫系统的遗传缺陷，他们在移植后存活了1至9个月。我们使用免疫细胞化学（利用神经元特异性抗体）和荧光原位杂交组织化学相结合，寻找Y染色体阳性细胞。在研究的所有四名患者中，我们在几个大脑区域发现了含有Y染色体的细胞。其中大多数是非神经元细胞（内皮细胞和白色物质中的细胞），但神经元确实被标记，特别是在海马和大脑皮层。最年轻的患者（2岁），移植后存活时间最长，供体来源的神经元数量最多（7/10，000）。标记细胞的分布不均匀。有Y阳性细胞簇，表明单个祖细胞经历克隆扩增和分化。我们的结论是，成年人骨髓细胞可以进入大脑并像啮齿动物细胞一样产生神经元。也许这种现象可以用来预防神经退行性疾病的发展或进展，或者修复因梗塞或创伤而受损的组织。
Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. Because we have demonstrated previously that transplanted bone marrow cells can enter the brain of mice and differentiate into neurons there, we decided to examine postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. We used a combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome-positive cells. In all four patients studied we found cells containing Y chromosomes in several brain regions. Most of them were nonneuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. We conclude that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma.