ArticleJournal of the American Heart Association2016
Allogeneic Mesenchymal Stromal Cells Overexpressing Mutant Human Hypoxia-Inducible Factor 1-α (HIF1-α) in an Ovine Model of Acute Myocardial Infarction.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- miR-199a-5p inhibited HIF-1α to suppress the proliferation, migration, and differentiation of cardiac stem cells.European journal of histochemistry : EJH · 2025Article
- Research Progress on Using Nanoparticles to Enhance the Efficacy of Drug Therapy for Chronic Mountain Sickness.Pharmaceutics · 2024Review
- HypoxamiR-210-3p regulates mesenchymal stem cells proliferation via P53 & Akt.Molecular and cellular biochemistry · 2024Article
- Review
- Advancements and Innovative Strategies in Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Therapy: A Comprehensive Review.Stem cells international · 2024Review
- Delivery of Growth Factors to Enhance Bone Repair.Bioengineering (Basel, Switzerland) · 2023Review
- Pathological implications of cellular stress in cardiovascular diseases.The international journal of biochemistry & cell biology · 2023Review
- Promoting early neovascularization by allotransplanted adipose-derived Muse cells in an ovine model of acute myocardial infarction.PloS one · 2023Article
- Cell-Based HIF1α Gene Therapy Reduces Myocardial Scar and Enhances Angiopoietic Proteome, Transcriptomic and miRNA Expression in Experimental Chronic Left Ventricular Dysfunction.Frontiers in bioengineering and biotechnology · 2022Article
- Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?Emerging topics in life sciences · 2021Review
- Nanotechnology in cardiac stem cell therapy: cell modulation, imaging and gene delivery.RSC advances · 2021Review
- Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering.Nanomaterials (Basel, Switzerland) · 2021Review
- Neovascularization: The Main Mechanism of MSCs in Ischemic Heart Disease Therapy.Frontiers in cardiovascular medicine · 2021Review
- Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration.International journal of molecular sciences · 2020Review
- Article
- Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness.Stem cell reviews and reports · 2020Review
- Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application.Stem cell research & therapy · 2020Review
- Mechanism of the hypoxia inducible factor 1/hypoxic response element pathway in rat myocardial ischemia/diazoxide post‑conditioning.Molecular medicine reports · 2020Article
- Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.Frontiers in cell and developmental biology · 2020Review
- Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities.Theranostics · 2020Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundBone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-α (HIF1-α), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-α would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. METHODS AND
resultsAllogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-α (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7±1.3% (P<0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P<0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-α-transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF.
conclusionsIntramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic.
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Registered trials
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