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Int. J. Mol. Sci. 2016, 17(7), 1082; doi:10.3390/ijms17071082

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

1
Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, via E. Chianesi 53, Rome 00144, Italy
2
Department of Surgical Science, Policlinico Umberto I, University of Rome “La Sapienza”, Viale Regina Elena 324, Rome 00161, Italy
3
Institute of General Pathology, Laboratory of Cell Signaling, Università Cattolica School of Medicine, Largo F. Vito 1, Rome 00168, Italy
These authors contributed equally to this work
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Muraca
Received: 26 May 2016 / Revised: 17 June 2016 / Accepted: 28 June 2016 / Published: 7 July 2016
(This article belongs to the Special Issue Advances in Cell Transplantation)
View Full-Text   |   Download PDF [3226 KB, uploaded 7 July 2016]   |  

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. View Full-Text
Keywords: adipose tissue-derived stromal and vascular cells; bioluminescence imaging; cell therapy; cell survival; cell transplantation; hypoxia; manganese superoxide dismutase; oxidative stress; reactive oxygen species adipose tissue-derived stromal and vascular cells; bioluminescence imaging; cell therapy; cell survival; cell transplantation; hypoxia; manganese superoxide dismutase; oxidative stress; reactive oxygen species
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Baldari, S.; Di Rocco, G.; Trivisonno, A.; Samengo, D.; Pani, G.; Toietta, G. Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase. Int. J. Mol. Sci. 2016, 17, 1082.

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