• 来稿:陈琳   北京市虹天济神经科学研究院

  • PLoS Med. 2007  Feb;4(2):e39.

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  • Extensive neuronal differentiation of  human neural stem cell grafts in adult rat spinal  cord

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  • Yan J, Xu L, Welsh AM, Hatfield G, Hazel  T, Johe K, Koliatsos VE.

  • Department of Pathology, Division of  Neuropathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of  America.

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  • BACKGROUND:  Effective treatments for degenerative and traumatic diseases of the nervous  system are not currently available. The support or replacement of injured  neurons with neural grafts, already an established approach in experimental  therapeutics, has been recently invigorated with the addition of neural and  embryonic stem-derived precursors as inexhaustible, self-propagating  alternatives to fetal tissues. The adult spinal cord, i.e., the site of common  devastating injuries and motor neuron disease, has been an especially  challenging target for stem cell therapies. In most cases, neural stem cell  (NSC) transplants have shown either poor differentiation or a preferential  choice of glial lineages.

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  • METHODS AND FINDINGS: In  the present investigation, we grafted NSCs from human fetal spinal cord grown in  monolayer into the lumbar cord of normal or injured adult nude rats and observed  large-scale differentiation of these cells into neurons that formed axons and  synapses and established extensive contacts with host motor neurons. Spinal cord  microenvironment appeared to influence fate choice, with centrally located cells  taking on a predominant neuronal path, and cells located under the pia membrane  persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than  one-tenth of grafted neurons differentiated into oligodendrocytes. The presence  of lesions increased the frequency of astrocytic phenotypes in the white matter.  

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  • CONCLUSIONS:  NSC grafts can show substantial neuronal differentiation in the normal and  injured adult spinal cord with good potential of integration into host neural  circuits. In view of recent similar findings from other laboratories, the extent  of neuronal differentiation observed here disputes the notion of a spinal cord  that is constitutively unfavorable to neuronal repair. Restoration of spinal  cord circuitry in traumatic and degenerative diseases may be more realistic than  previously thought, although major challenges remain, especially with respect to  the establishment of neuromuscular connections.


血管内皮生长因子体内刺激骨骼肌再生
优化可塑性:移植介导的脑修复中与环境和训练相关的因素

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成年大鼠脊髓中人A体神经干细胞移植的广泛神经分化