Regulating stem cell differentiation by controlling matrix elasticity
AssigneeThe Trustees of the University of Pennsylvania
InventorsAdam Engler, H. Sweeney, Dennis Discher
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Abstract
Provided are methods for the selection and regulation of the mechanical properties of substrates or tissue microenvironments as a technique to regulate in vitro differentiation, cell shape and/or lineage commitment of anchorage-dependent cells, such as mesenchymal stem cells into, e.g., neurogenic-, myogenic-, and osteogenic-type cells. Substrate mechanical properties include elasticity, tension, adhesion, and myosin-based contractile mechanisms. Inhibitors can be introduced to further regulate differentiation.
Claims19
A method for regulating differentiation and cell shape of an anchorage-dependent cell, comprising:
- selecting, designing, or engineering a substrate or tissue microenvironment having an elasticity defined by elastic constant E;
- introducing the anchorage-dependent cell onto a substrate or into a microenvironment;
- and
- developing the anchorage-dependent cell into a differentiated cell type, wherein shape and lineage commitment (in terms of gene or protein expression, or both) are regulated by the elasticity of the underlying substrate.
A method for regulating differentiation and cell shape of an anchorage-dependent cell, said method comprising:
- selecting, designing, or engineering a substrate or tissue microenvironment having an elasticity defined by elastic constant E;
- introducing the anchorage-dependent cell onto the substrate;
- and
- balancing chemo-mechanical energetics localized to cell adhesions against contractile energetics of the cell, σ, that balances cell traction stresses, τ, exerted by the cell on its underlying substrate, thereby controlling cell shape and lineage commitment.
Dependencies are inferred from the claim text.