Control of three-dimensional substrate stiffness to manipulate mesenchymal stem cell fate toward neuronal or glial lineages

The unlimited self-renewal and multipotency of stem cells provide great potential for applications in tissue engineering and regenerative medicine. The differentiation of stem cells can be induced by multiple factors including physical, chemical and biological cues. The fate of stem cells can be man...

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Bibliographic Details
Published in:Acta biomaterialia 2013-02, Vol.9 (2), p.5170-5180
Main Authors: Her, Goh Jih, Wu, Hsi-Chin, Chen, Ming-Hong, Chen, Ming-Yi, Chang, Shun-Chih, Wang, Tzu-Wei
Format: Article
Language:English
Subjects:
3-D scaffold
Biomarkers - metabolism
Cell Adhesion - drug effects
Cell Culture Techniques
Cell Differentiation
Cell Lineage - drug effects
Cell Proliferation
Collagen - pharmacology
Cross-Linking Reagents - chemistry
Elastic Modulus - drug effects
Humans
Hyaluronic Acid - pharmacology
Immunohistochemistry
Mechanical Phenomena - drug effects
Mechanical property
Mesenchymal stem cell
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - ultrastructure
Nerve tissue engineering
Neuroglia - cytology
Neuroglia - drug effects
Neuroglia - metabolism
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Porosity
Substrate stiffness
Tissue Scaffolds - chemistry
Water - chemistry
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Summary:The unlimited self-renewal and multipotency of stem cells provide great potential for applications in tissue engineering and regenerative medicine. The differentiation of stem cells can be induced by multiple factors including physical, chemical and biological cues. The fate of stem cells can be manipulated by deliberately controlling the interaction between stem cells and their microenvironment. The purpose of this study is to investigate the change in matrix stiffness under the influence of neurogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, three-dimensional (3-D) porous scaffolds were synthesized by type I collagen (Col) and hyaluronic acid (HA). The elastic modulus of the 3-D substrates was modified by adjusting the concentration of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC) as a crosslinking agent. The mechanical properties of Col–HA scaffolds were evaluated and the induction and characterization of hMSC differentiation toward neural lineages on substrates with different stiffnesses were studied. Using EDC of different concentrations for crosslinking, the stiffness of the matrices can be controlled in the range of 1–10kPa for soft to stiff substrates, respectively. The results showed that MSCs were likely to differentiate into neuronal lineage in substrate at 1kPa, while they transformed into glial cells in matrix at 10kPa. The morphology and proliferation behavior of hMSCs responded to the different stiffnesses of substrates. Using this modifiable matrix, we can investigate the relationship between stem cell behavior and substrate mechanical properties in extracellular matrix-based biomimetic 3-D scaffolds. A substrate with controllable stiffness capable of inducing hMSCs specifically toward neuronal differentiation may be very useful as a tissue-engineered construct or substitute for delivering hMSCs into the brain and spinal cord.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2012.10.012