Yeatts Andrew B, Choquette Daniel T, Fisher John P
Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Biochim Biophys Acta. 2013 Feb;1830(2):2470-80. doi: 10.1016/j.bbagen.2012.06.007. Epub 2012 Jun 15.
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. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
间充质干细胞（MSCs）是骨和软骨组织工程中一种很有前景的细胞来源，因为它们可以很容易地从体内分离出来，并分化为成骨细胞和软骨细胞。使用间充质干细胞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，这些支架的大小以及它们能够支持的细胞数量可能会受到限制。因此，生物反应器系统中的动态培养为体外培养和分化间充质干细胞提供了一种很有前景的方法。
本综述旨在描述关键的间充质干细胞分化信号通路，并提供证据说明动态培养如何增强这些通路。在概述动态培养系统之后，将讨论这些系统如何有效地调节和维持重要的培养参数，包括氧气含量和剪切应力。对文献进行了综述，以突出关键信号通路，并提供通过动态培养系统调节这些信号通路的证据。
了解这些培养系统如何影响间充质干细胞信号通路的能力，可能会带来一种剪切或氧气条件来引导干细胞分化。通过这种方式，间充质干细胞在三维支架上的体外培养和分化效率可能会大大提高。
生物反应器系统有能力控制许多关键的分化刺激因素，包括机械应力和氧气含量。在动态培养系统中进一步整合细胞信号研究，将更快地实现组织工程和再生医学的前景。本文是名为“干细胞生物化学”的特刊的一部分。
