正常大鼠脊髓或者受损伤大鼠脊髓中,人神经干细胞移植物(Human neural stem cell grafts)可以进行神经分化。研究结果刊登于《公共科学图书馆&;医学》(PLoS Medicine)。
先前研究人员一直认为,脊髓不支持来源于干细胞移植物的神经元分化。约翰霍普金斯大学和Neuralstem有限公司的研究人员,在Vassilis Koliatsos的带领下,将起源于某八周龄胎儿脊髓的神经干细胞移植物嫁接到正常或者受损的免疫缺陷成年大鼠的lower脊髓中。结果证实这些细胞,一些长出轴突,一些可以与宿主的运动神经细胞形成突触,显然,新的研究结果是对先前观点的挑战。
在这些发现被应用于临床之前,仍有很长的一段路要走。比如,尽管研究人员利用神经元特异细胞标记识别干细胞起源的细胞,但是并没有证明这些细胞的神经元功能(如产生电冲动),另外也没有研究实验大鼠的运动功能是否恢复。
Albany 医学院Sally Temple和Natalia Lowry在一篇相关评论文章中着重指出,需要在其它人类胚胎脊髓细胞所建立的各种原代细胞中,在各种非免疫缺陷的动物模型中重复此项工作,以及对实验动物动作进行分析等进一步研究。
Extensive Neuronal Differentiation of HumanNeural Stem Cell Grafts in Adult Rat Spinal Cord
Abstract
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.
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 onetenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter.
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.
英文全文链接:http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040039
