骨髓基质细胞微环境诱导神经干细胞的分化

Differentiation of neural stem cells induced by bone marrow stromal microenvironment

学术背景:骨髓基质细胞能够表达多种细胞表面分子及分泌多种细胞生长因子,其共同组成的微环境可以调节造血干细胞的分化和发育。造血干细胞和神经干细胞可表达很多共同基因,提示二者存在类似的发育和分化机制。目的:深入认识骨髓基质细胞提供的微环境对神经干细胞的诱导分化作用。检索策略:由该论文的研究人员应用计算机检索Pubmed数据库1992-01/2007-03的相关文献,检索词"bonemarrowstemcells,microenvironment,neuralstemcells,differentiation",并限定文章语言种类为English。同时计算机检索CHKD期刊全文数据库1994-01/2006-12的相关文献,检索词"骨髓基质细胞,神经干细胞,分化",并限定文章语言种类为中文。共检索到125篇文献,对资料进行初审,纳入标准:①文章所述内容应与骨髓基质细胞密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准:①重复性研究。②Meta分析。文献评价:文献来源主要是通过对骨髓基质细胞所提供的微环境诱导神经干细胞分化方面的内容进行汇总分析。所选用的31篇文献中,7篇为综述,其余均为临床或基础实验研究。资料综合:①骨髓基质细胞易于分离培养,其分泌的各种细胞因子、生长因子和细胞外基质成分所构成的微环境能够调节神经干细胞的发育和分化。②从mRNA水平看,骨髓基质细胞不仅有脑源性神经生长因子和神经生长因子的表达,还有胶质细胞源性神经营养因子的表达。从蛋白水平看,采用ELISA法在骨髓基质细胞的培养液和细胞蛋白中均可检测到胶质细胞源性神经营养因子。在生理状态下,骨髓基质细胞能分泌具有神经营养活性的物质,对损伤的运动神经元具有保护作用。此外研究证实骨髓基质细胞分泌至细胞外的可溶性物质具有直接调节神经干细胞分化的能力。结论:骨髓基质细胞通过分泌各种细胞因子所构成的微环境能够调节神经干细胞的发育,并诱导其向神经元方向分化。神经干细胞增殖分化的调控是非常复杂的过程,各因子间可能存在协同或拮抗作用,具体作用机制以及细胞信号转导通路还需深入研究。

BACKGROUND： The cell surface molecules are expressed and the cell growth factors are excreted by bone marrow stromal cell （BMSCs）, which consisting the microenvironment can regulate the differentiation and development of hemopoietic stem cells （HSCs）. Both HSCs and neural stem cells （NSCs） express many collaborating genes, indicating that those two kinds of cells have analogous mechanism of differentiation and development. OBJECTIVE： To know more about the effect of microenvironment provided by BMSCs on regulating the differentiation of NSCs. RETRIEVE STRATEGY： A computer-based search for the English articles in Pubmed published from January 1992 to March 2007 was undertaken, with the key words ＂bone marrow stem cells, microenvironment, neural stem cells, differentiation＂. CHKD database was also searched for the related articles published from January 1994 to December 2006, with the key words ＂bone marrow stromal cells, neural stem cells, microenvironment＂ in Chinese. Totally 125 related articles were collected after the primary trial. Inclusive criteria： ①the articles were closely related to BMSCs.②the articles in the same domain published on authority journals or in the near future were preferred. Exclusive criteria： ① repeated research.②Meta analysis. LITERATURE EVALUATION： Literature reference was the collected analysis of the articles about the microenvironment provided by BMSCs regulated the differentiation of NSCs. Among the 31 reference articles, 7 were reviews while the others were clinical or basic empirical studies. DATA SYNTHESIS： ①BMSCs are easier for isolated culture and have the function to regulate the differentiation and maturation of NSCs depending on the microenvironment provided by BMSCs, which consist of various cytokines, growth factors and extracellular matrix. ② The expressions of brain-derived neurotropic factor, nerve growth factor and gliocyte-derived neurotropic factor can be detected in BMSCs referring to mRNA. While there are gliocyte-derived neurotropic factor found in the culture medium of BMSCs and cell protein. Physiologically BMSCs can prevent the damaged motor neuron by excreting active neurotrophy substance. Additionally BMSCs are proved to regulate the differentiation of NSCs through the extracellular soluble substance. CONCLUSION： The microenvironment provided by BMSCs can be used to regulate the differentiation of NSCs to neurons, and this process is extremely complex, with the possible coordination or antagonistic action among the factors. Thus the action mechanism and cell signal transduction pathway need further investigations.