title: Scaffold-based transplantation of vascular endothelial growth factor-overexpressing stem cells leads to neovascularization in ischemic myocardium but did not show a functional regenerative effect.
abstract: The transplantation of skeletal myoblasts (SkM) might improve cardiac function after myocardial infarction via paracrine action. We used scaffold-based cell transfer by using vascular endothelial growth factor (VEGF)-overexpressing myoblasts. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were transfected with pCINeo-VEGF(121) and seeded on polyurethane (PU) scaffolds. The seeded scaffolds were epicardially implanted in rats 2 weeks after myocardial infarction (group: PU-VEGF-SkM). Before this intervention and 6 weeks later, pressure/volume loops were analyzed followed by histology. Additional study groups (n = 10 per group) were injected with VEGF-overexpressing myoblasts (Inj-VEGF-SkM) or unmodified myoblasts (Inj-SkM) or underwent a sham operation. Overexpression of VEGF was verified in vitro. The transplantation of growth factor producing myoblast-seeded scaffolds resulted in enhanced angiogenesis of ischemically damaged myocardium in vivo. However, the infarction size was not reduced. In group Inj-SkM, hemodynamics remained unchanged. Systolic function as measured by dP/dt(max) was not significantly altered in PU-VEGF-SkM (preinterventionally 2,156 ± 1,222 mmHg vs. postinterventionally 2,134 ± 850 mmHg). Other systolic function and diastolic function parameters as measured by dP/dt(min), tau, and pressure half-time were not restored in groups PU-VEGF-SkM and Inj-VEGF-SkM either. Transplantation of VEGF-overexpressing skeletal myoblasts leads to neovascularization in infarcted hearts. No functional myocardial recovery was observed. Scaffold-based transfer of genetically-modified cells remains a useful tool to study paracrine stem cell action.
authors.affiliation: Department of Cardiovascular Surgery, University Hospital Medical Center Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: von Wattenwyl
authors.forename: Britta
authors.initials: B
authors.lastname: Blumenthal
authors.forename: Claudia
authors.initials: C
authors.lastname: Heilmann
authors.forename: Peter
authors.initials: P
authors.lastname: Golsong
authors.forename: Annika
authors.initials: A
authors.lastname: Poppe
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Matthias
authors.initials: M
authors.lastname: Siepe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D015316:Genetic Therapy; D008297:Male; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A