TY - JOUR
T1 - Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
AU - Baldari, Silvia
AU - Di Rocco, Giuliana
AU - Trivisonno, Angelo
AU - Samengo, Daniela Maria
AU - Pani, Giovambattista
AU - Toietta, Gabriele
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - adipose tissue-derived stromal and vascular cells
KW - bioluminescence imaging
KW - cell survival
KW - cell therapy
KW - cell transplantation
KW - hypoxia
KW - manganese superoxide dismutase
KW - oxidative stress
KW - reactive oxygen species
KW - adipose tissue-derived stromal and vascular cells
KW - bioluminescence imaging
KW - cell survival
KW - cell therapy
KW - cell transplantation
KW - hypoxia
KW - manganese superoxide dismutase
KW - oxidative stress
KW - reactive oxygen species
UR - http://hdl.handle.net/10807/84856
U2 - 10.3390/ijms17071082
DO - 10.3390/ijms17071082
M3 - Article
SN - 1422-0067
VL - 17
SP - 1082
EP - 1093
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -