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Integrin‐linked kinase production prevents anoikis in human mesenchymal stem cells
Author(s) -
Benoit Danielle S.W.,
Tripodi Margaret C.,
Blanchette James O.,
Langer Steve J.,
Leinwand Leslie A.,
Anseth Kristi S.
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31292
Subject(s) - anoikis , integrin linked kinase , mesenchymal stem cell , protein kinase b , microbiology and biotechnology , self healing hydrogels , materials science , cancer research , signal transduction , chemistry , biology , kinase , protein kinase a , biochemistry , programmed cell death , apoptosis , polymer chemistry , cyclin dependent kinase 2
Abstract 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 (∼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. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007