Matrix Elasticity Directs Stem Cell Lineage Specification

  title={Matrix Elasticity Directs Stem Cell Lineage Specification},
  author={Adam J. Engler and Shamik Sen and H. Lee Sweeney and Dennis E. Discher},

Matrix Elasticity Directs Stem Cell Fates – How Deeply Can Cells Feel?

Naive mesenchymal stem cells from human bone marrow will be shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue level elasticity, which has significant implications for understanding physical effects of the in vivo microenvironment around cells.

Rewiring mesenchymal stem cell lineage specification by switching the biophysical microenvironment

This study demonstrates that MSCs remain susceptible to the biophysical properties of the extracellular matrix—even after several weeks of culture—and can redirect lineage specification in response to changes in the microenvironment.

Matrix Stiffness Modulates Mesenchymal Stem Cell Sensitivity to Geometric Asymmetry Signals

Insight gained from this study provides a rational basis for designing stem cell cultures to enhance tissue engineering and regenerative medicine strategies.

Elongated cell morphology and uniaxial mechanical stretch contribute to physical attributes of niche environment for MSC tenogenic differentiation

It is hypothesize that both enforced elongated cell morphology and uniaxial mechanical stretch signal contribute to the major physical niche attributes of tenocytes' in vivo microenvironment, and mimicking these physical signals may be sufficient to induce tenogenic differentiation of MSCs.

Intrinsic extracellular matrix properties regulate stem cell differentiation.

Extracellular Matrix Regulation of Stem Cell Fate

This review summarizes engineering approaches that have exploited natural and synthetic biomaterials to understand ECM regulation of stem cell fate and demonstrates how these studies have advanced the understanding of vascular maturation and mesenchymal lineage specification.

Regulating osteogenesis and adipogenesis in adipose‐derived stem cells by controlling underlying substrate stiffness

A range of polydimethylsiloxane‐based matrices with differing degrees of stiffness were generated and a comprehensive understanding of how stem cells respond to the surrounding microenvironment was provided, pointing to the fact that matrix stiffness is a critical element in biomaterial design and this will be an important advance in stem cell‐based tissue engineering.

Substrate Stiffness Directs Diverging Vascular Fates.

Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation

A review of a number of recent studies on how cell adhesion and mechanical cues influence the differentiation of MSCs into specific lineages shows evidence that mechanical signals played important roles in regulating a stem cell fate.

Factors Direct the Mesenchymal Stem Cell Lineage Commitment Reproductive Stem Cell Differentiation : Extracellular Matrix , Tissue Microenvironment , and Growth

The mesenchymal stem cells have awakened interest in regenerative medicine due to its high capability to proliferate and differentiate in multiple specialized lineages under defined conditions, and protocols of reproductive MSCs differentiation must be established.



Directing osteogenic and myogenic differentiation of MSCs: interplay of stiffness and adhesive ligand presentation.

The modulation of myogenic and osteogenic transcription factors by various ECM proteins demonstrates that substrate stiffness alone does not direct stem cell lineage specification, which has important implications in the development of tailored biomaterial systems that more closely mimic the microenvironment found in native tissues.

Substrate modulus directs neural stem cell behavior.

This work demonstrates that the mechanical and biochemical properties of an aNSC microenvironment can be tuned to regulate the self-renewal and differentiation of aN SCs.

Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery

Marrow stromal cells constitute an easily accessible, easily expandable source of cells that may prove useful in the establishment of spinal cord repair protocols and possibly effects on functional outcome in animals rendered paraplegic.

The regulation of osteogenesis by ECM rigidity in MC3T3‐E1 cells requires MAPK activation

A role for MAPK in the regulation of osteogenic differentiation by ECM compliance is confirmed by assessing the differentiation of MC3T3‐E1 cells cultured on poly(ethylene glycol)‐based model substrates with tunable mechanical properties.

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.

Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: Disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype

The ability of cultured rat MSC to undergo in vitro osteogenesis, chondrogenesis, and adipogenesis is confirmed, demonstrating differentiation of these cells to three mesenchymal cell fates, and changes in morphology upon addition of the chemical induction medium were caused by rapid disruption of the actin cytoskeleton.

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

The observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on–off switching of neural‐specific genes.

Adhesion-contractile balance in myocyte differentiation

Myotubes in culture are clearly prestressed by myosin II, and this contractility couples to substrate compliance and ultimately influences actomyosin striation, which implies a greater contractile stress.