Bioreactors to influence stem cell fate: Augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems

• Published in: Biochimica et biophysica acta Vol. 1830; no. 2; pp. 2470 - 2480
• Main Authors: Yeatts, Andrew B., Choquette, Daniel T., Fisher, John P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2013
• Subjects: Bioreactor; Bioreactors; cartilage; cell differentiation; Cell Lineage; Cell signaling; chondrocytes; Culture Media; dynamics; in vitro culture; Mesenchymal stem cell; osteoblasts; oxygen; Oxygen tension; Shear; shear stress; signal transduction; signals; stem cells; Stem Cells - cytology; Stem Cells - metabolism; tissue engineering; Mesenchymal stem cell; Bioreactor; Shear; Oxygen tension; Cell signaling
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.06.007

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. ► Perfusion bioreactors can regulate MSC exposure to shear stress and oxygen tension ► Shear stress and oxygen tension can enhance MSC differentiation pathways ► Bioreactors can be used to regulate oxygen and shear to direct MSC differentiation