title: Adenoviral transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.
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.
authors.affiliation: College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Treacy
authors.forename: Aideen E
authors.initials: AE
authors.lastname: Ryan
authors.forename: Teresa
authors.initials: T
authors.lastname: Heinzl
authors.forename: Lisa
authors.initials: L
authors.lastname: O'Flynn
authors.forename: Marese
authors.initials: M
authors.lastname: Cregg
authors.forename: Mieszko
authors.initials: M
authors.lastname: Wilk
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.forename: Paul
authors.initials: P
authors.lastname: Lohan
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.forename: Mikhail
authors.initials: M
authors.lastname: Nosov
authors.forename: Thomas
authors.initials: T
authors.lastname: Ritter
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007109:Immunity / Q000276:immunology*; D016130:Immunophenotyping; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D012333:RNA, Messenger; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors