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

doi:10.1016/j.actbio.2012.10.012

Cited by 171 publications

(131 citation statements)

References 40 publications

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“…In addition, the cell behavior in terms of cell differentiation or proliferation strongly depends on the cell maturation. Consistent with the observations of Hera et al [24], our findings illustrate that cells might need a longer time to become fully mature within force-free substrates (see Fig. 4) which is another reason for quicker cell fate achievement within forceinduced substrates.…”

Section: Discussionsupporting

confidence: 92%

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Numerical modeling of cell differentiation and proliferation in force-induced substrates via encapsulated magnetic nanoparticles

Mousavi

Doweidar

2016

Computer Methods and Programs in Biomedicine

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Cell migration, differentiation, proliferation and apoptosis are the main processes in tissue regeneration. Mesenchymal Stem Cells (MSCs) have the potential to differentiate into many cell phenotypes such as tissue-or organ-specific cells to perform special functions. Experimental observations illustrate that differentiation and proliferation of these cells can be regulated according to internal forces induced within their Extracellular matrix (ECM). The process of how exactly they interpret and transduce these signals is not well understood. Therefore, a previously developed three-dimensional (3D) computational model is here extended and employed to study how force-free substrates (FFS) and force-induced substrate (FIS) control cell differentiation and/or proliferation during the mechanosensing process. Consistent with experimental observations, it is assumed that cell internal deformation (a mechanical signal) in correlation with the cell maturation state directly triggers cell differentiation and/or proliferation. ECM is modeled as Neo-Hookean hyperelastic material assuming that cells are cultured within 3D nonlinear hydrogels. In agreement with wellknown experimental observations, the findings here indicate that within neurogenic (0.1-1 kPa), chondrogenic (20-25 kPa) and osteogenic (30-45 kPa) substrates, MSC differentiation and cell proliferation can be precipitated by inducing the substrate with an internal force. Therefore, cells require a longer time to grow and maturate within force-free substrates than withen force-induced substrates. In the instance of MSC differentiation into a compatible phenotype, the magnitude of the net traction force increases within chondrogenic and osteogenic substrates while it reduces within neurogenic substrates. This is consistent with experimental studies and numerical works recently published by the same authors. However, in all cases the magnitude of the net traction force considerably increases at the instant of cell proliferation because of cell-cell interaction. Consequently, the present model provides new perspectives to delineate the role of force-induced substrates in remotely controlling the cell fate during cell-matrix interaction, which open the door for new tissue regeneration methodologies.

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Section: Discussionsupporting

confidence: 92%

“…Experimental observations demonstrate that MSC culture within substrates resembling neurogenic tissue leads to neural precursor cells [13,24]. As in the previous examples, the results starting from the instant of cell differentiation are presented.…”

Section: Msc Lineage Specification Within Force-free and Forceinducedmentioning

confidence: 80%

Numerical modeling of cell differentiation and proliferation in force-induced substrates via encapsulated magnetic nanoparticles

Mousavi

Doweidar

2016

Computer Methods and Programs in Biomedicine

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“…Synthetic materials such as polycaprolactone, polyethylene glycol, and even polystyrene have been used as scaffolds for cell adherence and support [5,19,20]. Another method for scaffold-based neural cell culture provides cells with natural ECM proteins such as laminin or collagen [3,21,22]. Type I collagen with hyaluronic acid and alginate with laminin are some examples of natural material combinations used as cell scaffolds [3,21].…”

Section: Methods For 3d Cell Culturementioning

confidence: 99%

“…Another method for scaffold-based neural cell culture provides cells with natural ECM proteins such as laminin or collagen [3,21,22]. Type I collagen with hyaluronic acid and alginate with laminin are some examples of natural material combinations used as cell scaffolds [3,21]. Matrigel is another natural material that has been used extensively.…”

Section: Methods For 3d Cell Culturementioning

confidence: 99%

“…In 2D cell culture, cells are forced to adhere to a flat, hard plastic, or glass surface. These unfamiliar mechanical cues and lack of 3D extracellular matrix (ECM) support can have a significant impact on cellular behavior, function, growth, and morphology [2][3][4][5]. With the complexities of the nervous system, these changes can greatly skew experimental outcomes.…”

Section: Introductionmentioning

confidence: 99%

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