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

Goh Jih Her, Hsi Chin Wu, Ming Hong Chen, Ming Yi Chen, Shun Chih Chang, Tzu Wei Wang

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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 1-10 kPa for soft to stiff substrates, respectively. The results showed that MSCs were likely to differentiate into neuronal lineage in substrate at 1 kPa, while they transformed into glial cells in matrix at 10 kPa. 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.

Original languageEnglish
Pages (from-to)5170-5180
Number of pages11
JournalActa Biomaterialia
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 1 2013
Externally publishedYes

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Neuroglia
Stiffness
Substrates
Stem Cells
Hyaluronic Acid
Scaffolds (biology)
Ethyldimethylaminopropyl Carbodiimide
Stem Cell Niche
Hyaluronic acid
Biomimetics
Regenerative Medicine
Elastic Modulus
Tissue Engineering
Collagen Type I
Collagen
Scaffolds
Crosslinking
Cues

Keywords

  • 3-D scaffold
  • Mechanical property
  • Mesenchymal stem cell
  • Nerve tissue engineering
  • Substrate stiffness

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Control of three-dimensional substrate stiffness to manipulate mesenchymal stem cell fate toward neuronal or glial lineages. / Her, Goh Jih; Wu, Hsi Chin; Chen, Ming Hong; Chen, Ming Yi; Chang, Shun Chih; Wang, Tzu Wei.

In: Acta Biomaterialia, Vol. 9, No. 2, 01.02.2013, p. 5170-5180.

Research output: Contribution to journalArticle

Her, Goh Jih ; Wu, Hsi Chin ; Chen, Ming Hong ; Chen, Ming Yi ; Chang, Shun Chih ; Wang, Tzu Wei. / Control of three-dimensional substrate stiffness to manipulate mesenchymal stem cell fate toward neuronal or glial lineages. In: Acta Biomaterialia. 2013 ; Vol. 9, No. 2. pp. 5170-5180.
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