ArticleHuman gene therapy methods2013
Induction of aberrant vascular growth, but not of normal angiogenesis, by cell-based expression of different doses of human and mouse VEGF is species-dependent.
Article in Human gene therapy methods, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Subretinal rAAV2-based VEGF-Trap gene therapy for neovascular age-related macular degeneration: Preclinical assessment and phase 1 trial results.Cell reports. Medicine · 2026Article
- Sulfated polysaccharide reprograms arterialized angiogenesis of endochondral ossification to rescue defective osteonecrosis therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Investigational New Drug-enabling studies to use genetically modified mesenchymal stromal cells in patients with critical limb ischemia.Stem cells translational medicine · 2025Article
- The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.European journal of immunology · 2025Article
- Fenestrated Endothelial Cells across Organs: Insights into Kidney Function and Disease.International journal of molecular sciences · 2024Review
- Targeting tumor vasculature to improve antitumor activity of T cells armed ex vivo with T cell engaging bispecific antibody.Journal for immunotherapy of cancer · 2023Article
- Targeting Angiotensin-Converting Enzyme-2/Angiotensin-(1-7)/Mas Receptor Axis in the Vascular Progenitor Cells for Cardiovascular Diseases.Molecular pharmacology · 2021Review
- Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells.Cell reports · 2020Article
- miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer.Cells · 2020Article
- CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer.Cell death & disease · 2019Article
- Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.Scientific reports · 2016Article
- VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications.Cell metabolism · 2016Article
- VEGF dose regulates vascular stabilization through Semaphorin3A and the Neuropilin-1+ monocyte/TGF-β1 paracrine axis.EMBO molecular medicine · 2015Article
- Transplantation of vascular endothelial growth factor 165‑transfected endothelial progenitor cells for the treatment of limb ischemia.Molecular medicine reports · 2015Article
- Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine.Frontiers in bioengineering and biotechnology · 2015Review
- Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Skeletal muscle tissue engineering: strategies for volumetric constructs.Frontiers in physiology · 2014Review
- Scaffold-based delivery of a clinically relevant anti-angiogenic drug promotes the formation of in vivo stable cartilage.Tissue engineering. Part A · 2013Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic angiogenesis by vascular endothelial growth factor (VEGF) gene delivery is an attractive approach to treat ischemia. VEGF remains localized around each producing cell in vivo, and overexpression of mouse VEGF(164) (mVEGF(164)) induces normal or aberrant angiogenesis, depending strictly on its dose in the microenvironment in vivo. However, the dose-dependent effects of the clinically relevant factor, human VEGF(165) (hVEGF(165)), are unknown. Here we exploited a highly controlled gene delivery platform, based on clonal populations of transduced myoblasts overexpressing specific VEGF levels, to rigorously compare the in vivo dose-dependent effects of hVEGF(165) and mVEGF(164) in skeletal muscle of severe combined immune deficient (SCID) mice. While low levels of both factors efficiently induced similar amounts of normal angiogenesis, only high levels of mVEGF(164) caused widespread angioma-like structures, whereas equivalent or even higher levels of hVEGF(165) induced exclusively normal and mature capillaries. Expression levels were confirmed both in vitro and in vivo by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). However, in vitro experiments showed that hVEGF(165) was significantly more effective in activating VEGF receptor signaling in human endothelial cells than mVEGF(164), while the opposite was true in murine endothelial cells. In conclusion, we found that, even though hVEGF is similarly efficient to the syngenic mVEGF in inducing angiogenesis at lower doses in a widely adopted and convenient mouse preclinical model, species-dependent differences in the relative activation of the respective receptors may specifically mask the toxic effects of high doses of the human factor.
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