骨髓來源干細(xì)胞(bone marrow-derived stem cells, BMSCs)因為能夠在正常和病理條件下產(chǎn)生多種器官中不同細(xì)胞群體而一直被視為一種細(xì)胞移植來源。對BMSCs的很多研究而言,，大多數(shù)都集中注意力于將BMSCs移植到大腦后面的小腦中,，而且都是致力于修復(fù)受損的大腦組織或者有助于恢復(fù)丟失的神經(jīng)功能。最近,，西班牙研究小組發(fā)現(xiàn)由于存在一種“可塑性”機(jī)制,，BMSCs移植到包括嗅球在內(nèi)的大腦其他區(qū)域時也能產(chǎn)生多種多樣的神經(jīng)細(xì)胞類型。2011年12月21日,，他們的研究結(jié)果發(fā)表《細(xì)胞移植》(Cell Transplanation)期刊上,，而且可以免費(fèi)在線下載。
西班牙薩拉曼卡大學(xué)Eduardo Weruaga博士是該研究的通訊作者,，他說,，“根據(jù)我們的了解，我們的研究是世界上首次報道這些BMSCs促成嗅覺神經(jīng)元形成,。我們第一次證實依賴于移植的區(qū)域和細(xì)胞特異性的因子,，在同一個動物中BMSCs以不同的方式促成中樞神經(jīng)系統(tǒng)形成。”
在這項研究中,，研究人員移植骨髓細(xì)胞到不同年齡階段遭受特異性神經(jīng)元群體退化的突變小鼠中,，然后把它們與進(jìn)行類似移植的健康對照小鼠進(jìn)行比較。他們發(fā)現(xiàn)在這兩種小鼠實驗小組中,，BMSCs數(shù)量和小鼠壽命都發(fā)生增加,。然而在移植后六周，在測試動物的嗅球中觀察到更多的骨髓來源小神經(jīng)膠質(zhì)細(xì)胞(microglial cell),，但是僧帽細(xì)胞(mitral cell)---一種神經(jīng)元,，是嗅覺系統(tǒng)的一部分---的退化仍然還在進(jìn)行。這種不同在小腦中沒有觀察到,，因為在那里細(xì)胞退化早就完成,。
Weruaga博士解釋道，“我們的發(fā)現(xiàn)證實退化情形的程度能夠加強(qiáng)招募骨髓來源的神經(jīng)元,。但是我們也是首次提供證據(jù)表明BMSCs能夠通過可塑性機(jī)制同時參與到大腦不同區(qū)域,，如對大腦中最大和最為精細(xì)的樹突狀神經(jīng)元之一的浦肯雅細(xì)胞(Purkinje cell)而言是細(xì)胞融合，而對嗅球中間神經(jīng)元(interneuron)而言則是分化”。
Weruaga博士注意到他們證實BMSCs與浦肯雅細(xì)胞發(fā)生融合,，但是令人意料之外的是,，他們發(fā)現(xiàn)神經(jīng)退化情形對BMSCs的行為沒有影響,。
他說,，“有意思的是，BMSCs的作用通過這兩種不同的可塑性機(jī)制得以發(fā)揮作用,，這就強(qiáng)烈地提示著可塑性機(jī)制可能被移植的區(qū)域和細(xì)胞類型特異性因子所調(diào)節(jié),。”(生物谷：towersimper編譯)
doi:10.3727/096368910X552826
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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.
