Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems.
Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems.
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DOI：
10.1016/j.bbagen.2012.06.007
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发表时间：
2013-02
影响因子：
3
通讯作者：
Fisher, John P.
中科院分区：
文献类型：
--
作者：
Yeatts, Andrew B.;Choquette, Daniel T.;Fisher, John P.
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是骨和软骨组织工程的重要细胞来源，它可以很容易地从体内分离并分化为成骨细胞和软骨细胞。使用MSC的基于细胞的组织工程策略通常涉及在三维支架上培养这些细胞;然而，在传统的静态培养中，这些支架的大小和它们可以支持的细胞群体可能受到限制。因此，在生物反应器系统中的动态培养提供了一种有前途的手段，在体外培养和分化的MSC。这篇综述旨在描述关键的MSC分化信号通路，并为动态培养如何增强这些通路提供证据。在动态培养系统的概述之后，将讨论这些系统如何有效地修改和维持重要的培养参数，包括氧含量和剪切应力。文献综述的重点是通过动态培养系统调节这些信号通路的关键信号通路和证据。了解这些培养系统如何影响MSC信号通路的能力可能会导致剪切或氧机制来指导干细胞分化。以这种方式，在三维支架上的MSC的体外培养和分化的功效可以大大增加。生物反应器系统有能力控制许多关键的分化刺激，包括机械应力和氧含量。在动态培养系统中进一步整合细胞信号研究将导致更快地实现组织工程和再生医学的承诺。
Mesenchymal stem cells (MSCs) are a promising cell source for bone and cartilage tissue engineering as they can be easily isolated from the body and differentiated into osteoblasts and chondrocytes. A cell based tissue engineering strategy using MSCs often involves the culture of these cells on three-dimensional scaffolds; however the size of these scaffolds and the cell population they can support can be restricted in traditional static culture. Thus dynamic culture in bioreactor systems provides a promising means to culture and differentiate MSCs in vitro. This review seeks to characterize key MSC differentiation signaling pathways and provides evidence as to how dynamic culture is augmenting these pathways. Following an overview of dynamic culture systems, discussion will be provided on how these systems can effectively modify and maintain important culture parameters including oxygen content and shear stress. Literature is reviewed for both a highlight of key signaling pathways and evidence for regulation of these signaling pathways via dynamic culture systems. The ability to understand how these culture systems are affecting MSC signaling pathways could lead to a shear or oxygen regime to direct stem cell differentiation. In this way the efficacy of in vitro culture and differentiation of MSCs on three-dimensional scaffolds could be greatly increased. Bioreactor systems have the ability to control many key differentiation stimuli including mechanical stress and oxygen content. The further integration of cell signaling investigations within dynamic culture systems will lead to a quicker realization of the promise of tissue engineering and regenerative medicine.
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