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dc.contributor.authorGomez-Mauricio, Guadalupe 
dc.contributor.authorMoscoso, Isabel 
dc.contributor.authorMartin-Cancho, Maria-Fernanda
dc.contributor.authorCrisostomo, Veronica
dc.contributor.authorPrat-Vidal, Cristina 
dc.contributor.authorBaez-Diaz, Claudia
dc.contributor.authorSánchez-Margallo, Francisco Miguel
dc.contributor.authorBernad, Antonio 
dc.date.accessioned2017-10-30T13:15:41Z
dc.date.available2017-10-30T13:15:41Z
dc.date.issued2016
dc.identifierISI:000380003300001
dc.identifier.citationStem Cell Res Ther. 2016; 7(1):94
dc.identifier.issn1757-6512
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5210
dc.description.abstractBackground: 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.
dc.description.sponsorshipWe are indebted to the Viral Vectors Unit (CNIC), the Cytometry Unit (CNIC), and the Microscopy Unit (CNIC) for advice in various studies, Diego Celdran (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 Autonoma de Madrid (S2010/BMD-2420), and the Ministry of Health (IF06/3757-1) the Ministry of Science and Innovation (CCMI08-1E-003) to FMSM.
dc.language.isoeng
dc.publisherBioMed Central (BMC) 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMesenchymal stem cells
dc.subjectHGF
dc.subjectIGF-1
dc.subjectAcute myocardial infarction
dc.subjectPorcine model
dc.subjectGene therapy
dc.subjectCell therapy
dc.subjectHEPATOCYTE GROWTH-FACTOR
dc.subjectELEVATION MYOCARDIAL-INFARCTION
dc.subjectRANDOMIZED PHASE-1 TRIAL
dc.subjectPROGENITOR CELLS
dc.subjectINTRACORONARY INJECTION
dc.subjectHEART-FAILURE
dc.subjectIN-VITRO
dc.subjectREPAIR
dc.subjectTHERAPY
dc.subjectACTIVATION
dc.titleCombined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27423905
dc.format.volume7
dc.identifier.doi10.1186/s13287-016-0350-z
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1186/s13287-016-0350-z
dc.identifier.journalStem Cell Research & Therapy
dc.repisalud.orgCNICCNIC::Grupos de investigación::Antiguos CNIC
dc.repisalud.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2015-70882-Res_ES
dc.rights.accessRightsopen accesses_ES


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