Cargando…

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

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 evaluate...

Descripción completa

Detalles Bibliográficos
Autores principales: Baldari, Silvia, Di Rocco, Giuliana, Trivisonno, Angelo, Samengo, Daniela, Pani, Giovambattista, Toietta, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964458/
https://www.ncbi.nlm.nih.gov/pubmed/27399681
http://dx.doi.org/10.3390/ijms17071082
_version_ 1782445114845560832
author Baldari, Silvia
Di Rocco, Giuliana
Trivisonno, Angelo
Samengo, Daniela
Pani, Giovambattista
Toietta, Gabriele
author_facet Baldari, Silvia
Di Rocco, Giuliana
Trivisonno, Angelo
Samengo, Daniela
Pani, Giovambattista
Toietta, Gabriele
author_sort Baldari, Silvia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4964458
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-49644582016-08-03 Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase Baldari, Silvia Di Rocco, Giuliana Trivisonno, Angelo Samengo, Daniela Pani, Giovambattista Toietta, Gabriele Int J Mol Sci Article 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. MDPI 2016-07-07 /pmc/articles/PMC4964458/ /pubmed/27399681 http://dx.doi.org/10.3390/ijms17071082 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baldari, Silvia
Di Rocco, Giuliana
Trivisonno, Angelo
Samengo, Daniela
Pani, Giovambattista
Toietta, Gabriele
Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title_full Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title_fullStr Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title_full_unstemmed Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title_short Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase
title_sort promotion of survival and engraftment of transplanted adipose tissue-derived stromal and vascular cells by overexpression of manganese superoxide dismutase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964458/
https://www.ncbi.nlm.nih.gov/pubmed/27399681
http://dx.doi.org/10.3390/ijms17071082
work_keys_str_mv AT baldarisilvia promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase
AT diroccogiuliana promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase
AT trivisonnoangelo promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase
AT samengodaniela promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase
AT panigiovambattista promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase
AT toiettagabriele promotionofsurvivalandengraftmentoftransplantedadiposetissuederivedstromalandvascularcellsbyoverexpressionofmanganesesuperoxidedismutase