Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

Giovambattista Pani, Daniela Maria Samengo, Silvia Baldari, Giuliana Di Rocco, Angelo Trivisonno, Gabriele Toietta

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

17 Citazioni (Scopus)

Abstract

Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs), suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2). Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.
Lingua originaleEnglish
pagine (da-a)1082-1093
Numero di pagine12
RivistaInternational Journal of Molecular Sciences
Volume17
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • adipose tissue-derived stromal and vascular cells
  • bioluminescence imaging
  • cell survival
  • cell therapy
  • cell transplantation
  • hypoxia
  • manganese superoxide dismutase
  • oxidative stress
  • reactive oxygen species

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