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Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation

Treacy, Oliver
; 
Ryan, Aideen E.
; 
Heinzl, Teresa
; 
O'Flynn, Lisa
; 
Cregg, Marese
; 
Wilk, Mieszko
; 
Odoardi, Francesca
; 
Lohan, Paul
; 
O'Brien, Timothy
; 
Nosov, Mikhail
... show 1 more
Repository DOI
Publication Date
2012-08-06
Keywords
functional chemokine receptors, mediated gene-transfer, stromal cells, dendritic cells, engraftment, migration, therapy, vectors, modulation, expression
Type
Article
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Citation
Treacy, Oliver; Ryan, Aideen E. Heinzl, Teresa; O'Flynn, Lisa; Cregg, Marese; Wilk, Mieszko; Odoardi, Francesca; Lohan, Paul; O'Brien, Timothy; Nosov, Mikhail; Ritter, Thomas (2012). Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation. PLoS ONE 7 (8),
Abstract
Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential which makes them attractive targets for regenerative medicine applications. However, to date, therapeutic success of MSC-therapy is limited and the genetic modification of MSCs using viral vectors is one option to improve their therapeutic potential. Ex-vivo genetic modification of MSCs using recombinant adenovirus (Ad) could be promising to reduce undesired immune responses as Ad will be removed before cell/tissue transplantation. In this regard, we investigated whether Ad-modification of MSCs alters their immunological properties in vitro and in vivo. We found that Ad-transduction of MSCs does not lead to up-regulation of major histocompatibility complex class I and II and co-stimulatory molecules CD80 and CD86. Moreover, Ad-transduction caused no significant changes in terms of pro-inflammatory cytokine expression, chemokine and chemokine receptor and Toll-like receptor expression. In addition, Ad-modification of MSCs had no affect on their ability to suppress T cell proliferation in vitro. In vivo injection of Ad-transduced MSCs did not change the frequency of various immune cell populations (antigen presenting cells, T helper and cytotoxic T cells, natural killer and natural killer T cells) neither in the blood nor in tissues. Our results indicate that Ad-modification has no major influence on the immunological properties of MSCs and therefore can be considered as a suitable gene vector for therapeutic applications of MSCs.
Funder
Publisher
Public Library of Science (PLoS)
Publisher DOI
10.1371/journal.pone.0042662
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland
cbn
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Externally hosted open access publications with University of Galway authors (2)