RT Journal Article
T1 Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model
A1 Gómez-Mauricio, Guadalupe
A1 Moscoso, Isabel
A1 Martín-Cancho, María-Fernanda
A1 Crisóstomo, Verónica
A1 Prat-Vidal, Cristina
A1 Báez Díaz, Claudia
A1 Sánchez-Margallo, Francisco M.
A1 Bernad, Antonio
K1 Mesenchymal stem cells
K1 HGF
K1 IGF-1
K1 Acute myocardial infarction
K1 Porcine model
K1 Gene therapy
K1 Cell therapy
AB BackgroundInsulin-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.MethodsPig 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.ResultsIntramyocardial 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.ConclusionsThe 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
PB BioMed Central
YR 2016
FD 2016-07-16
LK http://hdl.handle.net/10347/15969
UL http://hdl.handle.net/10347/15969
LA eng
NO Gómez-Mauricio et al. Stem Cell Research & Therapy (2016) 7:94 DOI 10.1186/s13287-016-0350-z
NO We are indebted to the Viral Vectors Unit (CNIC), the Cytometry Unit (CNIC), and the Microscopy Unit (CNIC) for advice in various studies, Diego Celdrán (CCMIJU) for conducting necropsies and anesthesia of the animals, Juan Maestre (CCMIJU) for conducting the NMR, Juan Camilo Estrada for providing the haMSC used in the karyotypes, and Catherine Mark for editorial assistance. This study was supported by funding from the European Commission (HEALTH-2009_242038) and the Instituto de Salud Carlos III (RETICS-RD12/0019/0018 and -RD06/0010/1014), and by grants to AB from the Spanish Ministry of Science and Innovation (SAF2012-34327; SAF2015-70882-R; PLE2009-0147), the Research Program of the Comunidad Autónoma de Madrid (S2010/BMD-2420), and the Ministry of Health (IF06/3757-1) the Ministry of Science and Innovation (CCMI08-1E-003) to FMSM
DS Minerva
RD 24 abr 2026