Biomimetic microenvironment modulates neural stem cell survival, migration, and differentiation.
Biomimetic microenvironment modulates neural stem cell survival, migration, and differentiation.
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DOI：
10.1089/ten.tea.2009.0837
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发表时间：
2010-09
影响因子：
--
通讯作者：
S. Stabenfeldt;Gautam Munglani;Andrés J. García;M. LaPlaca
中科院分区：
文献类型：
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作者：
S. Stabenfeldt;Gautam Munglani;Andrés J. García;M. LaPlaca
以受控的三维构型呈现细胞外基质（ECM）组分的生物材料基质提供了研究神经干细胞（NSC）-ECM相互作用的独特系统。我们培养原代小鼠神经球在甲基纤维素（MC）与层粘连蛋白-1（MC-x-LN 1）功能化的支架和监测神经干细胞的生存，凋亡，迁移，分化和基质的生产。总的来说，与MC对照相比，MC-x-LN 1增强了NSC的存活和成熟。通过bcl-2/bax基因表达和四甲基罗丹明-dUTP缺口末端标记，观察到MC-x-LN 1中的凋亡活性水平显著低于MC对照。在MC-x-LN 1中，以β 1-整合素介导的方式延伸神经突的NSC的百分比高于MC对照。此外，在MC-x-LN 1中的神经干细胞的分化概况表现出比MC对照中更高水平的神经元和少突胶质细胞前体标记物。在MC-x-LN 1中，LN 1的产生和与α <$β <$整合素的共定位显著增加，而在MC对照中，纤连蛋白的产生更明显。这些发现表明，NSC微环境调节整个神经球的细胞活动，有助于我们理解ECM介导的NSC行为，并为开发合理设计的神经移植信使提供新的途径。
Biomaterial matrices presenting extracellular matrix (ECM) components in a controlled three-dimensional configuration provide a unique system to study neural stem cell (NSC)-ECM interactions. We cultured primary murine neurospheres in a methylcellulose (MC) scaffold functionalized with laminin-1 (MC-x-LN1) and monitored NSC survival, apoptosis, migration, differentiation, and matrix production. Overall, MC-x-LN1 enhanced both NSC survival and maturation compared with MC controls. Significantly lower levels of apoptotic activity were observed in MC-x-LN1 than in MC controls, as measured by bcl-2/bax gene expression and tetramethylrhodamine-dUTP nick end labeling. A higher percentage of NSCs extended neurites in a β₁-integrin-mediated fashion in MC-x-LN1 than in MC controls. Further, the differentiation profiles of NSCs in MC-x-LN1 exhibited higher levels of neuronal and oligodendrocyte precursor markers than in MC controls. LN1 production and co-localization with α₆β₁ integrins was markedly increased within MC-x-LN1, whereas the production of fibronectin was more pronounced in MC controls. These findings demonstrate that NSC microenvironments modulate cellular activity throughout the neurosphere, contributing to our understanding of ECM-mediated NSC behavior and provide new avenues for developing rationally designed couriers for neurotransplantation.