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Integrin-linked kinase production preven ... in human mesenchymal stem cells
Integrin-linked kinase production prevents anoikis in human mesenchymal stem cells.
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Human mesenchymal stem cells (hMSCs) were infected with an adenovirus expressing integrin-linked kinase (ILK) to understand the role of cell-ECM signal transduction cascades in suppressing anoikis. Survivability of ILK-infected hMSCs encapsulated in poly(ethylene glycol) (PEG) hydrogels, an anoikis-inducing environment, was sustained at 90% over 7 weeks, and survival was attributed to increased protein kinase B (PKB/Akt) activation. hMSCs encapsulated in RGD-modified hydrogels induced an upregulation in ILK production, PKB/Akt activation, and subsequent survival to the same extent of ILK-infected, encapsulated hMSCs. As negative controls, encapsulated hMSCs were infected with cyclization recombinase (a protein not associated with cell survival)-expressing virus, and uninfected hMSCs exhibited very little ILK production, PKB/Akt activation, and survival ( approximately 55% after 7 weeks). As a measure of cell-matrix interactions, vinculin was also quantified for the encapsulated hMSCs and found to be 30-fold greater for cells encapsulated in RGD-modified hydrogels and fivefold greater for ILK-infected hMSCs than controls, indicating that cell-material interactions are inducing the cell survivability of hMSCs encapsulated in RGD-modified hydrogels. In sum, ILK infection can support cell survival in the absence of matrix interactions and enable fundamental studies of three-dimensional cell function in response to extrinsic signals, independently of matrix-ligand interactions.
Benoit DS, Tripodi MC, Blanchette JO, Langer SJ, Leinwand LA, Anseth KS
Journal of biomedical materials research. Part A
2007-05-01 00:00
81
2
259-68
Department of Chemical and Biological Engineering, University of Colorado, 424 UCB ECCH 111, Boulder, Colorado 80309, USA
NIDCR DE016523
1549-3296
10.1002/jbm.a.31292
736
True
17335036
