title: Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase.
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.
authors.affiliation: Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, via E. Chianesi 53, Rome 00144, Italy. silvia.baldari@yahoo.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baldari
authors.affiliation: Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, via E. Chianesi 53, Rome 00144, Italy. giuliana.dirocco@ifo.gov.it.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Di Rocco
authors.affiliation: Department of Surgical Science, Policlinico Umberto I, University of Rome "La Sapienza", Viale Regina Elena 324, Rome 00161, Italy. angelo.trivisonno@uniroma1.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Trivisonno
authors.affiliation: Institute of General Pathology, Laboratory of Cell Signaling, Universit&#224; Cattolica School of Medicine, Largo F. Vito 1, Rome 00168, Italy. daniela.samengo@libero.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Samengo
authors.affiliation: Institute of General Pathology, Laboratory of Cell Signaling, Universit&#224; Cattolica School of Medicine, Largo F. Vito 1, Rome 00168, Italy. Giovambattista.Pani@unicatt.it.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Pani
authors.affiliation: Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, via E. Chianesi 53, Rome 00144, Italy. gabriele.toietta@ifo.gov.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Toietta
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity; D005260:Female; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008163:Luminescent Measurements; D051379:Mice; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D003035:Cobalt; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C018021:cobaltous chloride
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