Dynamic compression and exogenous fibronectin regulates cell-matrix adhesions and intracellular signaling proteins of human mesenchymal stem cells in 3D collagen environment

2013 ◽  
Author(s):  
Chuen-wai Li
2011 ◽  
Vol 22 ◽  
pp. 214-225 ◽  
Author(s):  
O Schätti ◽  
◽  
S Grad ◽  
J Goldhahn ◽  
G Salzmann ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie A. Maynard ◽  
Ekaterina Pchelintseva ◽  
Limor Zwi-Dantsis ◽  
Anika Nagelkerke ◽  
Sahana Gopal ◽  
...  

AbstractClinical use of human mesenchymal stem cells (hMSCs) is limited due to their rapid clearance, reducing their therapeutic efficacy. The inflammatory cytokine IL-1β activates hMSCs and is known to enhance their engraftment. Consequently, understanding the molecular mechanism of this inflammation-triggered adhesion is of great clinical interest to improving hMSC retention at sites of tissue damage. Integrins are cell–matrix adhesion receptors, and clustering of integrins at the nanoscale underlies cell adhesion. Here, we found that IL-1β enhances adhesion of hMSCs via increased focal adhesion contacts in an α5β1 integrin-specific manner. Further, through quantitative super-resolution imaging we elucidated that IL-1β specifically increases nanoscale integrin α5β1 availability and clustering at the plasma membrane, whilst conserving cluster area. Taken together, these results demonstrate that hMSC adhesion via IL-1β stimulation is partly regulated through integrin α5β1 spatial organization at the cell surface. These results provide new insight into integrin clustering in inflammation and provide a rational basis for design of therapies directed at improving hMSC engraftment.


Author(s):  
Stephen D. Thorpe ◽  
Conor T. Buckley ◽  
Andrew J. Steward ◽  
Daniel J. Kelly

Unconfined cyclic compressive loading has been shown to promote the chondrogenic differentiation of agarose encapsulated mesenchymal stem cells (MSCs) in the absence of chondrogenic growth factors [1, 2]. However, in general robust chondrogenesis has not been reported as a result of mechanical stimulation alone; with biochemical stimulation through TGF-β supplementation yielding a more potent pro-chondrogenic effect [2, 3].


2006 ◽  
Vol 290 (3) ◽  
pp. C776-C784 ◽  
Author(s):  
Ryan C. Riddle ◽  
Amanda F. Taylor ◽  
Damian C. Genetos ◽  
Henry J. Donahue

Mechanical signals are important regulators of skeletal homeostasis, and strain-induced oscillatory fluid flow is a potent mechanical stimulus. Although the mechanisms by which osteoblasts and osteocytes respond to fluid flow are being elucidated, little is known about the mechanisms by which bone marrow-derived mesenchymal stem cells respond to such stimuli. Here we show that the intracellular signaling cascades activated in human mesenchymal stem cells by fluid flow are similar to those activated in osteoblastic cells. Oscillatory fluid flow inducing shear stresses of 5, 10, and 20 dyn/cm2 triggered rapid, flow rate-dependent increases in intracellular calcium that pharmacological studies suggest are inositol trisphosphate mediated. The application of fluid flow also induced the phosphorylation of extracellular signal-regulated kinase-1 and -2 as well as the activation of the calcium-sensitive protein phosphatase calcineurin in mesenchymal stem cells. Activation of these signaling pathways combined to induce a robust increase in cellular proliferation. These data suggest that mechanically induced fluid flow regulates not only osteoblastic behavior but also that of mesenchymal precursors, implying that the observed osteogenic response to mechanical loading may be mediated by alterations in the cellular behavior of multiple members of the osteoblast lineage, perhaps by a common signaling pathway.


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