title: Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity.
abstract: The most prominent capabilities of mesenchymal stem cells (MCSs) which make them promising for therapeutic applications are their capacity to endure and implant in the target tissue. However, the therapeutic applications of these cells are limited due to their early death within the first few days following transplantation. Therefore, to improve cell therapy efficacy, it is necessary to manipulate MSCs to resist severe stresses imposed by microenvironment. In this study, we manipulated MSCs to express a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2) to address this issue. Full-length human Nrf2 cDNA was isolated and TOPO cloned into TOPO cloning vector and then transferred to gateway adapted adenovirus expression vector by LR recombination reaction. Afterwards, the Nrf2 bearing recombinant virus was prepared in appropriate mammalian cell line and used to infect MSCs. The viability and apoptosis of the Nrf2 expressing MSCs were evaluated following hypoxic and oxidative stress conditions. Transient expression of Nrf2 by MSCs protected them against cell death and the apoptosis triggered by hypoxic and oxidative stress conditions. Nrf2 also enhanced the activity of SOD and HO-1. These findings could be used as a strategy for prevention of graft cell death in MSC-based cell therapy. It also indicates that management of cellular stress responses can be used for practical applications.
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mohammadzadeh
authors.forename: Raheleh
authors.initials: R
authors.lastname: Halabian
authors.forename: Ahmad
authors.initials: A
authors.lastname: Gharehbaghian
authors.forename: Naser
authors.initials: N
authors.lastname: Amirizadeh
authors.forename: Ali
authors.initials: A
authors.lastname: Jahanian-Najafabadi
authors.forename: Amaneh Mohammadi
authors.initials: AM
authors.lastname: Roushandeh
authors.forename: Mehryar Habibi
authors.initials: MH
authors.lastname: Roudkenar
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D015687:Cell Hypoxia; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase