title: Adenovirus-mediated expression of the HO-1 protein within MSCs decreased cytotoxicity and inhibited apoptosis induced by oxidative stresses.
abstract: The capacity of mesenchymal stem cells (MSCs) to survive and engraft in the target tissue may lead to promising therapeutic effects. However, the fact that the majority of MSCs die during the first few days following transplantation complicates cell therapy. Hence, it is necessary to strengthen the stem cells to withstand the rigors of the microenvironment to improve the efficacy of cell therapy. In this study, we manipulated MSCs to express a cytoprotective factor, heme oxygenase-1 (HO-1), to address this issue. Full-length cDNA of human HO-1 was isolated and cloned into TOPO vector by TOPO cloning reaction. Then, the construct was ligated to gateway adapted adenovirus expression vector by LR recombination reaction. Afterwards, the recombinant virus expressing HO-1 was produced in appropriate mammalian cell line and used to infect MSCs. The HO-1 engineered MSCs were exposed to hypoxic and oxidative stress conditions followed by evaluation of the cells' viability and apoptosis. Transient expression of HO-1 was detected within MSCs. It was observed that HO-1 expression could protect MSCs against cell death and the apoptosis triggered by hypoxic and oxidative stress conditions. The MSCs-HO-1 retained their ability to differentiate into adipogenic, chondrogenic, or osteogenic lineages. These findings could be applied as a strategy for prevention of graft cell death in MSCs-based cell therapy and is a good demonstration of how an understanding of cellular stress responses can be used for practical applications.
authors: Research Center, Iranian Blood Transfusion Organization, Tehran, Iran.
authors: Pejman
authors: P
authors: Hamedi-Asl
authors: Raheleh
authors: R
authors: Halabian
authors: Parisa
authors: P
authors: Bahmani
authors: Mahshid
authors: M
authors: Mohammadipour
authors: Mohammad
authors: M
authors: Mohammadzadeh
authors: Amaneh Mohammadi
authors: AM
authors: Roushandeh
authors: Ali
authors: A
authors: Jahanian-Najafabadi
authors: Yoshikazu
authors: Y
authors: Kuwahara
authors: Mehryar Habibi
authors: MH
authors: Roudkenar
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction
chemical_list: D051547:Heme Oxygenase-1