Roles of activated astrocytes in bone marrow stromal cell proliferation and differentiation
Roles of activated astrocytes in bone marrow stromal cell proliferation and differentiation
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DOI：
10.1016/j.neuroscience.2009.02.068
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发表时间：
2009-05
期刊：
影响因子：
3.3
通讯作者：
F.-W. Wang;De-yong Jia;Zhan‐hui Du;J. Fu;Shi-dan Zhao;S-m Liu;Y.-M. Zhang;E. Ling;A. Hao
中科院分区：
文献类型：
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作者：
F.-W. Wang;De-yong Jia;Zhan‐hui Du;J. Fu;Shi-dan Zhao;S-m Liu;Y.-M. Zhang;E. Ling;A. Hao
局部微环境在决定中枢神经系统（CNS）干细胞的命运选择中起着重要作用。星形胶质细胞是中枢神经系统局部微环境的主要组成部分，已被证明可以影响干细胞的增殖和神经分化，包括神经干/祖细胞、胚胎干细胞和骨髓基质细胞（BMSC）。然而，炎症激活的星形胶质细胞是否会影响骨髓间充质干细胞的行为仍有待确定。为此，本研究制备了星形胶质细胞条件培养基（ACM）用于治疗BMSCs。取自 Wistar 大鼠星形胶质细胞的 ACM 分别经脂多糖刺激 12、36 或 72 h，作为炎性 ACM（12 h ACM、36 h ACM 和 72 h ACM），而未刺激的星形胶质细胞则用作正常对照星形胶质细胞条件培养基（N-ACM）。结果显示，与N-ACM中生长的BMSC相比，在炎性ACM中生长的BMSC的增殖和神经分化显着增加。暴露于36小时ACM的BMSC的效率显着高于暴露于12或72小时ACM的BMSC的效率。中和ACM的白细胞介素6（IL-6）后，BMSCs的增殖和星形胶质细胞分化均下降；另一方面，神经元分化显着增加。目前的研究结果表明，炎症激活的星形胶质细胞可以促进BMSCs的增殖和神经分化，并且中枢神经系统损伤后不同时期激活的星形胶质细胞可能对BMSCs产生不同的影响。此外，星形胶质细胞来源的IL-6参与BMSC的增殖和神经分化。
Local microenvironment plays an important role in determining the fate choice of stem cells in the central nervous system (CNS). Astrocytes, a major component of local microenvironment in the CNS, have been demonstrated to influence the proliferation and neural differentiation of stem cells including neural stem/progenitor cells, embryonic stem cells and bone marrow stromal cells (BMSCs). However, it has remained to be ascertained if inflammation-activated astrocytes can affect the behavior of BMSCs. To this end, astrocyte-conditioned medium (ACM) was prepared in this study for treatment of BMSCs. The ACM derived from Wistar rat astrocytes stimulated by lipopolysaccharide for 12, 36 or 72 h, respectively, served as inflammatory ACM (12 h ACM, 36 h ACM and 72 h ACM), while that from unstimulated astrocytes was used as normal control astrocyte-conditioned medium (N-ACM). The results showed that the proliferation and neural differentiation of BMSCs grown in inflammatory ACM were significantly increased compared with those grown in N-ACM. The efficiency of BMSCs exposed to 36 h ACM was significantly greater than that of those exposed to 12 or 72 h ACM. Following neutralization of interleukin-6 (IL-6) of the ACM, both the proliferation and astrocytic differentiation of BMSCs were decreased; on the other hand, the neuronal differentiation was significantly increased. The present findings suggest that inflammation-activated astrocytes can facilitate the proliferation and neural differentiation of BMSCs and activated astrocytes at different phase after CNS injuries might have distinct effects on BMSCs. Moreover, astrocyte-derived IL-6 participates in the proliferation and neural differentiation of BMSCs.