Substrate stiffness and oxygen availability as regulators of mesenchymal stem cell differentiation within a mechanically loaded bone chamber

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• 作者：Darren Paul Burke (1) (2)
  Hanifeh Khayyeri (3)
  Daniel John Kelly (1) (2) (4)
  
• 关键词：Stem cell differentiation ; Finite element ; Bone chamber ; Tissue regeneration ; Substrate stiffness ; Oxygen availability
• 刊名：Biomechanics and Modeling in Mechanobiology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：14
• 期：1
• 页码：93-105
• 全文大小：2,835 KB
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• 作者单位：Darren Paul Burke (1) (2)
  Hanifeh Khayyeri (3)
  Daniel John Kelly (1) (2) (4)
  
  1. Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
  2. Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland
  3. Department of Biomedical Engineering, Lund University, Lund, Sweden
  4. Advanced Materials and Bioengineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland
  
• 刊物类别：Engineering
• 刊物主题：Theoretical and Applied Mechanics
  Biomedical Engineering
  Mechanics
  Biophysics and Biomedical Physics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1617-7940

文摘

Mechanical stimuli such as tissue deformation and fluid flow are often implicated as regulators of mesenchymal stem cell (MSC) differentiation during regenerative events in vivo. However, in vitro studies have identified several other physical and biochemical environmental cues, such as substrate stiffness and oxygen availability, as key regulators of stem cell fate. Hypotheses for how MSC differentiation is regulated in vivo can be either corroborated or rejected based on the ability of in silico models to accurately predict spatial and temporal patterns of tissue differentiation observed experimentally. The goal of this study was to employ a previously developed computational framework to test the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation during tissue regeneration within an implanted bone chamber. To enable a prediction of the oxygen levels within the bone chamber, a lattice model of angiogenesis was implemented where blood vessel progression was dependent on the local mechanical environment. The model successfully predicted key aspects of MSC differentiation, including the correct spatial development of bone, marrow and fibrous tissue within the unloaded bone chamber. The model also successfully predicted chondrogenesis within the chamber upon the application of mechanical loading. This study provides further support for the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation in vivo. These simulations also highlight the indirect role that mechanics may play in regulating MSC fate by inhibiting blood vessel progression and hence disrupting oxygen availability within regenerating tissues.