Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord
Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord
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DOI：
10.1073/pnas.0501029102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Glover, JC
中科院分区：
文献类型：
--
作者：
Sigurjonsson, OE;Perreault, MC;Glover, JC
造血干细胞（hematopoieticstemcells，HSCs）被认为是一种潜在的神经细胞来源，可用于脑损伤的修复，但以往的研究表明，HSCs的神经元分化率较低，且没有提供神经元表型的确切证据。为了测试人HSC的神经原性潜能，我们将来自成人骨髓的CD34+ HISCs植入鸡胚胎发育中的脊髓病变中，并通过免疫组织化学、逆行标记和电生理学来观察它们的分化。我们发现，来自植入群体的人类细胞表达神经元标记物NeuN和MAP 2的速率比以前报道的要高得多。我们还发现，这些细胞表现出神经元的细胞结构，延伸轴突到腹根或几个节段的长度内的脊髓白色的问题，装饰与synaptotagmin+和GABA+突触末梢，并表现出积极的膜特性和自发的突触电位的功能集成的神经元的特征。神经元分化伴随着CD34表达的丧失。用共聚焦显微镜仔细检查发现没有异核体的迹象，人类细胞从不表达鸡特异性抗原，这表明与宿主鸡细胞融合是不可能的。我们的结论是，在鸡胚胎脊髓再生的微环境刺激成年人HISCs分化成成熟的神经元的相当大的比例。这可能为从患者自己的骨髓中高产量生产神经元开辟新的可能性。
Hematopoietic stem cells (HSCs) have been proposed as a potential source of neural cells for use in repairing brain lesions, but previous studies indicate a low rate of neuronal differentiation and have not provided definite evidence of neuronal phenotype. To test the neurogenic potential of human HSCs, we implanted CD34+ HISCs from adult human bone marrow into lesions of the developing spinal cord in the chicken embryo and followed their differentiation by using immunohistochemistry, retrograde labeling, and electrophysiology. We find that human cells derived from the implanted population express the neuronal markers NeuN and MAP2 at substantially higher rates than previously reported. We also find that these cells exhibit neuronal cytoarchitecture, extend axons into the ventral roots or several segments in length within the spinal white matter, are decorated with synaptotagmin+ and GABA+ synaptic terminals, and exhibit active membrane properties and spontaneous synaptic potentials characteristic of functionally integrated neurons. Neuronal differentiation is accompanied by loss of CD34 expression. Careful examination with confocal microscopy reveals no signs of heterokaryons, and human cells never express a chicken-specific antigen, suggesting that fusion with host chicken cells is unlikely. We conclude that the microenvironment in the regenerating spinal cord of the chicken embryo stimulates substantial proportions of adult human HISCs to differentiate into full-fledged neurons. This may open new possibilities for a high-yield production of neurons from a patient's own bone marrow.