Chapter 7 Mechanobiology of Adult and Stem Cells

Wang, James H.‐C.; Thampatty, Bhavani P.

doi:10.1016/s1937-6448(08)01207-0

Cited by 100 publications

(83 citation statements)

References 218 publications

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“…12,13 In addition to surface topography, much research has also been focused on surface elasticity. The relationship between contractile forces and the mechanical elasticity, or stiffness, of extracellular matrices can have a major influence on cell behaviors, such as differentiation of stem cells, 2,14 migration, 15 apoptosis 16 and proliferation. 17 A previous study of a tunable hydrogel system, which is decorated with gold nanostructures and can be 'programmed' to assume varying degrees of stiffness, found that the adhesion and migration of plasmodium sporozoites is more efficient on stiff, bonelike interfaces than on soft, skin-like ones.…”

Section: Introductionmentioning

confidence: 99%

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

et al. 2016

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Cellular adhesion and growth on substrates with differing surface topography are known to induce unusual cell behaviors. Here, we investigated the adhesion and growth of human embryonic kidney 293T cells on vertically aligned silicon nanowires. Varying the diameter of nanowires affected their elasticity, which in turn caused variations in cell morphology and adhesion. Calculation of their elastic modulus revealed that long and thin nanowires are easier to deflect and thus provide more focal adhesion sites for adherent cells. And, induced mechanical tension triggered cellular anisotropic growth in the direction of tension, creating a greater rate of filopodium growth than was observed with a bare glass substrate devoid of mechanical tension. This nanotopographical approach provides important insights into the role of artificial substrates in the modulation of cell behavior and a conceptual framework for further analysis of substrate-induced changes in cellular activity.

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Section: Introductionmentioning

confidence: 99%

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

et al. 2016

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“…Once MSCs have reached the bone fracture site they are confronted with a challenging milieu characterised not only by inflammatory cytokines and low oxygen tension (hypoxia) but also by constant mechanical strain (Goodship and Kenwright, 1985;Komatsu and Hadjiargyrou, 2004). This condition is likely to affect MSCs, which are known to be mechanosensitive (Wang and Thampatty, 2008). Thus, detailed knowledge about the influence of mechanical loading on MSCs is pivotal for understanding the physiological processes during bone regeneration in order to develop innovative cell therapy approaches.…”

Section: Introductionmentioning

confidence: 99%

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

Ode

Schoon²,

Kurtz³

et al. 2013

eCM

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Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, β-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/ chondrogenic differentiation of MSCs and may provide a -thus far underestimated -therapeutic target to guide bone regeneration. Keywords IntroductionBone healing is a complex, however well-orchestrated, multistage regenerative process. Bone fracture coincides with disruption of blood vessels resulting in activation of the coagulation cascade and formation of the haematoma, which encloses the fracture area. Inflammatory cells, fibroblasts, and mesenchymal stromal cells (MSCs) are recruited to the site. Once MSCs have reached the bone fracture site they are confronted with a challenging milieu characterised not only by inflammatory cytokines and low oxygen tension (hypoxia) but also by constant mechanical strain (Goodship and Kenwright, 1985;Komatsu and Hadjiargyrou, 2004). This condition is likely to affect MSCs, which are known to be mechanosensitive (Wang and Thampatty, 2008). Thus, detailed knowledge about the influence of mechanical loading on MSCs is pivotal for understanding the physiological processes during bone regeneration in order to develop innovative cell therapy approaches.Recently, we and others provided evidence that mechanical strain leads to reduced expression of the cell surface marker CD73 in vitro (Kang et al., 2011;Ode et al., 2011). In our study, bone marrow (BM)-MSCs underwent cyclic-compressive loading for three days. CD73 protein a...

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“…Importantly, the latter condition likely affects MSCs, which are known to be mechanosensitive (Wang and Thampatty, 2008). Thus, detailed knowledge about the infl uence of mechanical loading on MSCs is pivotal for understanding (Kasper et al, 2007a) and matrix remodelling (Kasper et al, 2007b) -key processes in bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

Ode

Kopf²,

Kurtz³

et al. 2011

eCM

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The assumption that mesenchymal stromal cell (MSC)-based-therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo signifi cant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading.Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5'-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identifi ed as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration.These results suggest that MSC migration is controlled by CD73/CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfi l their regenerative functions.

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Chapter 7 Mechanobiology of Adult and Stem Cells

Cited by 100 publications

References 218 publications

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

CD73/5’-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

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