2026-07-21T07:44:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52102024-09-27T09:53:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Gomez-Mauricio, Guadalupe
author
Moscoso, Isabel
author
Martin-Cancho, Maria-Fernanda
author
Crisostomo, Veronica
author
Prat-Vidal, Cristina
author
Baez-Diaz, Claudia
author
Sánchez-Margallo, Francisco Miguel
author
Bernad, Antonio
funder
Unión Europea. Comisión Europea
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Ministerio de Ciencia e Innovación (España)
2017-10-30T13:15:41Z
2017-10-30T13:15:41Z
2016
Stem Cell Res Ther. 2016; 7(1):94
10.1186/s13287-016-0350-z
1757-6512
Stem Cell Research & Therapy
27423905
http://hdl.handle.net/20.500.12105/5210
Background: Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell-and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Methods: Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Results: Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1: 1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. Conclusions: The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.
eng
Mesenchymal stem cells
HGF
IGF-1
Acute myocardial infarction
Porcine model
Gene therapy
Cell therapy
HEPATOCYTE GROWTH-FACTOR
ELEVATION MYOCARDIAL-INFARCTION
RANDOMIZED PHASE-1 TRIAL
PROGENITOR CELLS
INTRACORONARY INJECTION
HEART-FAILURE
IN-VITRO
REPAIR
THERAPY
ACTIVATION
Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model
journal article
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e27e667b0d39b306b7d3ffa2548d78d8
2379762
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CombinedAdministrationOfMesenchymalStem_2016
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81fa4eddafc4aa3161e9b02881be47bc
80387
text/plain
CombinedAdministrationOfMesenchymalStem_2016.txt