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Cell Stress and Chaperones

, Volume 17, Issue 5, pp 553–565 | Cite as

Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity

  • Mohammad Mohammadzadeh
  • Raheleh Halabian
  • Ahmad Gharehbaghian
  • Naser Amirizadeh
  • Ali Jahanian-Najafabadi
  • Amaneh Mohammadi Roushandeh
  • Mehryar Habibi RoudkenarEmail author
Original Paper

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.

Keywords

Mesenchymal stem cells Nrf2 Adenoviral vector Oxidative stress Apoptosis 

Notes

Acknowledgments

We thank Professor Reinhard Dietrich Henschler (Head, Research and Development, German Red Cross Blood Donor Service Baden-Württemberg—Hessen) for his scientific support and providing some materials.

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Copyright information

© Cell Stress Society International 2012

Authors and Affiliations

  • Mohammad Mohammadzadeh
    • 1
  • Raheleh Halabian
    • 1
  • Ahmad Gharehbaghian
    • 2
  • Naser Amirizadeh
    • 1
  • Ali Jahanian-Najafabadi
    • 3
  • Amaneh Mohammadi Roushandeh
    • 4
  • Mehryar Habibi Roudkenar
    • 1
    Email author
  1. 1.Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion MedicineTehranIran
  2. 2.Medical Laboratory Sciences Department, School of Allied Medical SciencesShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Department of Molecular BiologyPasteur Institute of IranTehranIran
  4. 4.Department of Anatomy, Faculty of MedicineHamadan University of Medical SciencesHamadanIran

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