Peter Golsong

Publications (5)12.42 Total impact

• Article: 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.

  Robert von Wattenwyl, Britta Blumenthal, Claudia Heilmann, Peter Golsong, Annika Poppe, Friedhelm Beyersdorf, Matthias Siepe
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  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.
  ASAIO journal (American Society for Artificial Internal Organs: 1992) 05/2012; 58(3):268-74. · 1.39 Impact Factor
• Article: Hepatocyte growth factor-transfected skeletal myoblasts to limit the development of postinfarction heart failure.

  Annika Poppe, Peter Golsong, Britta Blumenthal, Robert von Wattenwyl, Philipp Blanke, Friedhelm Beyersdorf, Christian Schlensak, Matthias Siepe
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  ABSTRACT: Stem cells transplanted to an injured heart affect the host myocardium indirectly. The cytokine hepatocyte growth factor (HGF) may play a key role in this paracrine activity. We hypothesized that HGF-overexpressing stem cells would restore cardiac function after myocardial infarction (MI). Because there is a high rate of cell death when injecting the cells intramyocardially, we used scaffold-based cell transfer. Skeletal myoblasts (SkMs) were isolated and expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huHGF and seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection. The seeded scaffolds were transplanted in rats two weeks after MI (group: PU-HGF-SkM) or the infection solution was intramyocardially injected (group: Inj-HGF-SkM). Two groups (Inj-SkM and PU-SkM) have been prepared with untransfected cells and sham group without any cell therapy served as control (n = 10 each group). At the beginning of treatment (baseline) and six weeks later, hemodynamic parameters were assessed. At the end of the study, histological analysis was employed. In sham animals we detected a decrease in systolic and diastolic function during the observation time. Treatment with untransfected myoblasts did not lead to any significant changes in hemodynamic parameters between the intervention and six weeks later. In group PU-HGF-SkM, systolic parameters like dP/dt(max), dP/dt(min) and isovolumic contraction improved significantly from baseline to study end. Some diastolic parameters were inferior as compared to baseline (SB-Ked, pressure half time [PHT], Tau). In group Inj-HGF-SkM, only PHT was impaired as compared to preinterventional values. Histological analysis showed significantly more capillaries in the infarction border zone in groups PU-HGF-SkM than in sham and Inj-SkM group. The infarction size was not affected by the therapy. Transplanting HGF-transfected myoblasts after MI can limit the development of ventricular dysfunction. Scaffold-based therapy in combination with gene therapy accelerates this capacity. This hemodynamic amelioration is accompanied by neovascularization, but not by smaller infarction sizes.
  Artificial Organs 09/2011; 36(3):238-46. · 2.00 Impact Factor
• Article: Functional regeneration of ischemic myocardium by transplanted cells overexpressing stromal cell-derived factor-1 (SDF-1): intramyocardial injection versus scaffold-based application.

  Britta Blumenthal, Annika Poppe, Peter Golsong, Philipp Blanke, Bartosz Rylski, Friedhelm Beyersdorf, Christian Schlensak, Matthias Siepe
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  ABSTRACT: Stromal cell-derived factor-1 (SDF-1) is a potent chemotaxin. Increased SDF-1 levels can be found in ischemic myocardium and might protect against ischemia-reperfusion injury. We hypothesized that transplantation of stem cells overexpressing SDF-1 might improve cardiac function after myocardial infarction (MI). We compared intramyocardial injection with a scaffold-based application of SDF-1-transfected cells. Skeletal myoblasts (SkMs) were isolated and expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huSDF-1 and seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection. Two weeks after myocardial infarction, seeded scaffolds were implanted epicardially into rats (group: PU-SDF-1-SkM) or the injection solution was applied intramyocardially (Inj-SDF-1-SkM). Additional groups were treated with non-transfected myoblasts either by injection (Inj-SkM) or by scaffold-based application (PU-SkM) or received a sham operation (Sham). Before this intervention and 6 weeks later, hemodynamic parameters were measured. Infarction size and neovascularization were assessed by histology at study end. In sham animals, we detected a clear decrease in systolic function from intervention to study end. In group Inj-SkM and PU-SkM, all hemodynamic parameters that were assessed remained unchanged during observation time. Systolic function as measured by dP/dt(max) and SB-Emax was significantly improved in groups Inj-SDF-1-SkM and PU-SDF-1-SkM at study end without a difference between the two SDF-1 groups. Diastolic function measured by post-interventional dP/dt(min) was also increased in group Inj-SDF-1-SkM but not in PU-SDF-1-SkM. Histological analysis revealed a reduced infarction size in all treatment groups at study end but enhanced neovascularization was not observable. Transplantation of myoblasts overexpressing SDF-1 improves cardiac function after MI. The restoration of hemodynamic parameters is accompanied by a reduction in infarction size. This reverse remodeling capacity is independent of a scaffold-based application of the SDF-1-transfected cells.
  European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 06/2011; 40(4):e135-41. · 2.40 Impact Factor
• Article: Scaffold-based transplantation of akt1-overexpressing skeletal myoblasts: functional regeneration is associated with angiogenesis and reduced infarction size.

  Matthias Siepe, Peter Golsong, Annika Poppe, Britta Blumenthal, Robert von Wattenwyl, Claudia Heilmann, Katharina Förster, Christian Schlensak, Friedhelm Beyersdorf
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  ABSTRACT: Myoblast-based therapy can improve cardiac function after infarction and is conventionally performed by direct injection. A scaffold-based transfer could overcome injection-associated problems. In upgrading this approach we transplanted skeletal myoblasts (SkM) overexpressing the prosurvival gene Akt1. SkM were transfected with pcDNA3-huda-Akt1 and seeded on polyurethane scaffolds. These scaffolds were transplanted in rats 2 weeks after myocardial infarction. Hemodynamics were analyzed before therapy and 6 weeks later. Infarction size and capillary density were performed thereafter. Additional groups received injections of Akt1-transfected or untransfected myoblasts, scaffolds seeded with untransfected myoblasts, or sham operation. Deterioration of global systolic left ventricular function could be inhibited by all therapeutic approaches. In addition, transplantation of Akt1-transfected cells, either scaffold-based or injected, was superior with regard to systolic properties of the left ventricular wall. This effect was accompanied by smaller infarction sizes and angiogenesis. Scaffolds with untransfected myoblasts yielded also smaller infarctions than injections of untransfected myoblasts. Both Akt groups profited with regard to dP/dt(min). In contrast, other diastolic parameters pointed at impaired relaxation and stiffer myocardium especially in the Akt1-scaffold group. In conclusion, SkM overexpressing Akt1 can maintain myocardial function after infarction, reduce infarction size, and induce neovascularization. Scaffold-based cell transfer does not augment this reverse remodeling capacity.
  Tissue Engineering Part A 01/2011; 17(1-2):205-12. · 4.64 Impact Factor
• Article: Polyurethane scaffolds seeded with genetically engineered skeletal myoblasts: a promising tool to regenerate myocardial function.

  Britta Blumenthal, Peter Golsong, Annika Poppe, Claudia Heilmann, Christian Schlensak, Friedhelm Beyersdorf, Matthias Siepe
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  ABSTRACT: In animal models, intramyocardial injection of primary skeletal myoblasts is supposed to promote tissue regeneration and to improve cardiac function after myocardial infarction. The usage of genetically engineered myoblasts overexpressing the paracrine factors involved in tissue repair is believed to enhance these effects. However, cell therapy via injection is always accompanied by a high death rate of the injected cells. Here, we describe the construction of a growth factor-producing myoblast-seeded scaffold to overcome this limitation. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were seeded on polyurethane (PU) scaffolds (Artelon) and transfected with DNA of VEGF-A, HGF, SDF-1, or Akt1 using the lipid-based Metafectene Pro method. Overexpression was verified by ELISA, RT-PCR (VEGF-A, HGF, and SDF-1) and Western blot analysis (Akt1). The seeded scaffolds were transplanted onto damaged myocardium of Lewis rats 2 weeks after myocardial infarction. Six weeks later, their therapeutic potential in vivo was analyzed by measurement of infarction size and capillary density. Primary rat skeletal myoblasts seeded on PU scaffolds were efficiently transfected, achieving transfection rates of 20%. In vitro, we noted a significant increase in expression of VEGF-A, HGF, SDF-1, and Akt1 after transfection. In vivo, transplantation of growth factor-producing myoblast-seeded scaffolds resulted in enhanced angiogenesis (VEGF-A, HGF, and Akt1) or a reduced infarction zone (SDF-1 and Akt1) in the ischemically damaged myocardium. In summary, we constructed a growth factor-producing myoblast-seeded scaffold which combines the beneficial potential of stem cell transplantation with the promising effects of gene-therapeutic approaches. Because this matrix also allows us to circumvent previous cell application drawbacks, it may represent a promising tool for tissue regeneration and the re-establishment of cardiac function after myocardial infarction.
  Artificial Organs 02/2010; 34(2):E46-54. · 2.00 Impact Factor