Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model
| Autor: | Isabel Moscoso, Guadalupe Gómez-Mauricio, Cristina Prat-Vidal, María F. Martín-Cancho, Claudia Báez-Díaz, Verónica Crisóstomo, Francisco M. Sánchez-Margallo, Antonio Bernad |
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| Přispěvatelé: | European Commission, Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RANDOMIZED PHASE-1 TRIAL INTRACORONARY INJECTION Swine medicine.medical_treatment Cell- and Tissue-Based Therapy Myocardial Infarction Gene Expression Medicine (miscellaneous) HEPATOCYTE GROWTH-FACTOR THERAPY Cell therapy Neovascularization ACTIVATION Genes Reporter Fibrosis Transgenes HGF Insulin-Like Growth Factor I Porcine model Hepatocyte Growth Factor IGF-1 Molecular Medicine HEART-FAILURE Female Hepatocyte growth factor Stem cell medicine.symptom medicine.drug Green Fluorescent Proteins Neovascularization Physiologic Acute myocardial infarction Mesenchymal Stem Cell Transplantation Biochemistry Genetics and Molecular Biology (miscellaneous) 03 medical and health sciences Gene therapy medicine Animals Humans Regeneration Progenitor cell REPAIR business.industry Myocardium Research Growth factor Mesenchymal stem cell ELEVATION MYOCARDIAL-INFARCTION Mesenchymal Stem Cells Cell Biology IN-VITRO medicine.disease Disease Models Animal 030104 developmental biology PROGENITOR CELLS Immunology Cancer research Mesenchymal stem cells business |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) Stem Cell Research & Therapy Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela instname |
| Popis: | 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 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 SI |
| Databáze: | OpenAIRE |
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