骨髓来源干细胞(bone marrow-derived stem cells, BMSCs)因为能够在正常和病理条件下产生多种器官中不同细胞群体而一直被视为一种细胞移植来源。对BMSCs的很多研究而言，大多数都集中注意力于将BMSCs移植到大脑后面的小脑中，而且都是致力于修复受损的大脑组织或者有助于恢复丢失的神经功能。最近，西班牙研究小组发现由于存在一种“可塑性”机制，BMSCs移植到包括嗅球在内的大脑其他区域时也能产生多种多样的神经细胞类型。2011年12月21日，他们的研究结果发表《细胞移植》(Cell Transplanation)期刊上，而且可以免费在线下载。
西班牙萨拉曼卡大学Eduardo Weruaga博士是该研究的通讯作者，他说，“根据我们的了解，我们的研究是世界上首次报道这些BMSCs促成嗅觉神经元形成。我们第一次证实依赖于移植的区域和细胞特异性的因子，在同一个动物中BMSCs以不同的方式促成中枢神经系统形成。”
在这项研究中，研究人员移植骨髓细胞到不同年龄阶段遭受特异性神经元群体退化的突变小鼠中，然后把它们与进行类似移植的健康对照小鼠进行比较。他们发现在这两种小鼠实验小组中，BMSCs数量和小鼠寿命都发生增加。然而在移植后六周，在测试动物的嗅球中观察到更多的骨髓来源小神经胶质细胞(microglial cell)，但是僧帽细胞(mitral cell)---一种神经元，是嗅觉系统的一部分---的退化仍然还在进行。这种不同在小脑中没有观察到，因为在那里细胞退化早就完成。
Weruaga博士解释道，“我们的发现证实退化情形的程度能够加强招募骨髓来源的神经元。但是我们也是首次提供证据表明BMSCs能够通过可塑性机制同时参与到大脑不同区域，如对大脑中最大和最为精细的树突状神经元之一的浦肯雅细胞(Purkinje cell)而言是细胞融合，而对嗅球中间神经元(interneuron)而言则是分化”。
Weruaga博士注意到他们证实BMSCs与浦肯雅细胞发生融合，但是令人意料之外的是，他们发现神经退化情形对BMSCs的行为没有影响。
他说，“有意思的是，BMSCs的作用通过这两种不同的可塑性机制得以发挥作用，这就强烈地提示着可塑性机制可能被移植的区域和细胞类型特异性因子所调节。”(生物谷：towersimper编译)
doi:10.3727/096368910X552826
PMC:
PMID:
Bone Marrow Contributes Simultaneously to Different Neural Types in the Central Nervous System Through Different Mechanisms of Plasticity
Recio, Javier S.; Álvarez-Dolado, Manuel; Díaz, David; Baltanás, Fernando C.; Piquer-Gil, Marina; Alonso, José R.; Weruaga, Eduardo
Many studies have reported the contribution of bone marrow-derived cells (BMDC) to the CNS, raising the possibility of using them as a new source to repair damaged brain tissue or restore neuronal function. This process has mainly been investigated in the cerebellum, in which a degenerative microenvironment has been suggested to be responsible for its modulation. The present study further analyzes the contribution of BMDC to different neural types in other adult brain areas, under both physiological and neurodegenerative conditions, together with the mechanisms of plasticity involved. We grafted genetically marked green fluorescent protein/Cre bone marrow in irradiated recipients: a) the PCD (Purkinje Cell Degeneration) mutant mice, suffering a degeneration of specific neuronal populations at different ages, and b) their corresponding healthy controls. These mice carried the conditional lacZ reporter gene to allow the identification of cell fusion events. Our results demonstrate that BMDC mainly generate microglial cells, although to a lesser extent a clear formation of neuronal types also exists. This neuronal recruitment was not increased by the neurodegenerative processes occurring in PCD mice, where BMDC did not contribute to rescuing the degenerated neuronal populations either. However, an increase in the number of bone marrow-derived microglia was found along the life span in both experimental groups. Six weeks after transplantation more bone marrow-derived microglial cells were observed in the olfactory bulb of the PCD mice compared to the control animals, where the degeneration of mitral cells was in process. In contrast, this difference was not observed in the cerebellum, where Purkinje cell degeneration had been completed. These findings demonstrated that the degree of neurodegenerative environment can foster the recruitment of neural elements derived from bone marrow, but also provide the first evidence that BMDC can contribute simultaneously to different encephalic areas through different mechanisms of plasticity: cell fusion for Purkinje cells and differentiation for olfactory bulb interneurons.
