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Synergistic effect of combined intramyocardial CD34+ cells and VEGF2 gene therapy after MI
- Source :
- Nature Clinical Practice Cardiovascular Medicine. 3:S123-S128
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- Previous studies have shown that local angiogenic gene therapy acts, in part, by recruiting endothelial progenitor cells (EPCs) to ischemic tissue. Recent data indicate that patients with the most severe vascular disease may have insufficient or deficient EPCs and the poorest response to angiogenic therapy. Accordingly, we hypothesized that combining human CD34(+) cell implantation with local vascular endothelial growth factor 2 (phVEGF2) gene therapy might overcome these deficiencies. The addition of VEGF2 to EPC cultures resulted in significant and dose-dependent decreases in EPC apoptosis. Phosphorylated Akt (p-Akt) was increased in VEGF2-treated EPCs. In vivo, myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in 34 immunodeficient rats. The animals were then randomized to one of four treatment groups: cell therapy alone with human CD34(+) cells; VEGF2 gene therapy alone; combination therapy with CD34(+) cells plus phVEGF2; or CD34(-) cells and 50 microg empty plasmid. Four weeks after MI, animals treated with combination therapy showed improved fractional shortening, increased capillary density, and reduced infarct size compared with the other three groups. Combination therapy was also associated with an increased number of circulating EPCs 1 week after MI. Combined subtherapeutic doses of cell and gene therapy result in a significant therapeutic effect compared to monotherapy. This approach may overcome therapeutic failures (e.g. inability of certain patients to mobilize sufficient EPCs) and may also offer safety advantages by allowing lower dosing strategies.
- Subjects :
- Combination therapy
Genetic enhancement
Myocardial Infarction
CD34
Antigens, CD34
Apoptosis
Pharmacology
Transplantation, Autologous
Cell therapy
Rats, Nude
chemistry.chemical_compound
Animals
Medicine
Progenitor cell
Cells, Cultured
Dose-Response Relationship, Drug
Vascular Endothelial Growth Factors
business.industry
Vascular disease
Myocardium
Endothelial Cells
Genetic Therapy
General Medicine
medicine.disease
Combined Modality Therapy
Rats
Vascular endothelial growth factor
Transplantation
Disease Models, Animal
chemistry
Immunology
cardiovascular system
Female
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 17434300 and 17434297
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Nature Clinical Practice Cardiovascular Medicine
- Accession number :
- edsair.doi.dedup.....c1671a142e2528f10f9ca72bb282c7c6