Integrin-linked kinase production prevents anoikis in human mesenchymal stem cells

✍ Scribed by Danielle S.W. Benoit; Margaret C. Tripodi; James O. Blanchette; Steve J. Langer; Leslie A. Leinwand; Kristi S. Anseth

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 978 KB
• Volume: 81A
• Category: Article
• ISSN: 1549-3296
• DOI: 10.1002/jbm.a.31292

✦ Synopsis

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