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Table 1 Examples of biophysical regulation within the stem cell niche

From: Biophysical regulation of stem cell behavior within the niche

Biophysical property

Stimulus

Cell type

Response

References

Ligand-substrate immobilization

VEGF; EGF; Shh; NT-3, PDGF; LIF, SCF

Human endothelial cells; rat hepatocytes; rat MSCs; hESC-derived NPCs; mESCs

VEGFR2 activation; DNA synthesis; osteoblast differentiation; decreased astrogensis; STAT3/MAPK activation

[9]; [10]; [11]; [12]; [13]

Multivalent presentation

Galactose; RGD; Hh; TGF-β; Shh

Escherichia coli; mouse fibroblasts; Drosophila; mink lung epithelial cells; mouse embryonic C3H10T1/2 cells

Chemotaxis; motility/adhesion; patched activation; endocytosis; osteogenic differentiation

[16]; [18]; [20]; [21]; [24]

Surface topography

70- to 100-nm nanotubes; nanotopographical disorder; 350-nm gratings; decreased collagen-anchoring sites

hMSCs; hMSCs; hMSCs; human epidermal stem cells

Osteoblast differentiation; bone ECM formation; decreased zyxin/increased motility; increased differentiation

[25]; [26]; [27]; [49]

Physical orientation of stem cells

450-μm cell cluster size/150-μm cell cluster size; decreased cell colony size

mESCs; hESCs

Cardiogenesis/endothelial cell differentiation; increased endodermal differentiation

[31]; [32]

Elastic modulus

Soft/hard matrix; decreased substrate stiffness; increased ECM stiffness; decreased/increased matrix rigidity; substrate stiffness gradient; soft hydrogel substrates; soft substrates

hMSCs; rat NPCs; hPSCs; murine mammary gland cells; hMSCs; mMuSCs; mESCs

Neurogenesis/osteogenesis; increased neuronal differentiation; increased cell and colony spreading; TGF-β1-induced apoptosis/EMT; migration up stiffness gradient; self-renewal and in vivo regeneration; homogeneous self-renewal and downregulated cell tractions

[37]; [38]; [39]; [40]; [41]; [43]; [44]

Dynamic mechanical forces

Local cell traction on non-linear elastic fibrin gel; cell compression; cell-cortex tension; stretch-induced TIP-1/TIP-3 expression; cyclic biaxial strain; equiaxial/uniaxial strain; dynamic hydrogel stiffening; shear stress; shear stress; laminar shear stress; fluid shear stress

hMSCs; Drosophila germ cells; zebrafish; lung EMCs; hESCs; human bone marrow MSCs; chicken cardiomyocytes; hEPCs; mEMCs; mESCs; mESCs

Global matrix stiffening; Twist protein expression; progenitor-cell sorting; myogenesis/adipogenesis; increased TGFβ1/Activin A/Nodal expression; SM α-actin and SM-22α downregulation/upregulation; increased cardiac maturation; proliferation, differentiation, and vascular tube formation; endothelial differentiation; epigenetic histone modification and cardiovascular lineage programming; differentiation into vascular endothelial cells

[42]; [50]; [51]; [52]; [53]; [54]; [58]; [61]; [62]; [63]; [64]

  1. ECM, extracellular matrix; EGF, epidermal growth factor; EMC, embryonic mesenchymal cell; EMT, epithelial-mesenchymal transition; hEPC, human endothelial progenitor cell; hESC, human embryonic stem cell; Hh, hedgehog; hMSC, human mesenchymal stem cell; hPSC, human pluripotent stem cell; LIF, leukemia inhibitory factor; MAPK, mitogen-activated protein kinase; mEMC, mouse embryonic mesenchymal cell; mESC, mouse embryonic stem cell; mMuSC, mouse muscle stem cell; MSC, mesenchymal stem cell; NPC, neural progenitor cell; NT-3, neurotrophic factor 3; PDGF, platelet-derived growth factor; RGD, arginine-glycine-asparagine peptide; SCF, stem cell factor; Shh, sonic hedgehog; SM, smooth muscle; STAT3, signal transducer and activator of transcription 3; TGF-β, transforming growth factor-beta; TIP, tension-induced/inhibited protein; VEGF, vascular endothelial growth factor; VEGFR2, vascular endothelial growth factor receptor 2.