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1.
Hum Gene Ther Methods ; 23(5): 346-56, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23075102

ABSTRACT

Vascular endothelial growth factor (VEGF) can induce normal angiogenesis or the growth of angioma-like vascular tumors depending on the amount secreted by each producing cell because it remains localized in the microenvironment. In order to control the distribution of VEGF expression levels in vivo, we recently developed a high-throughput fluorescence-activated cell sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a specific VEGF dose from a heterogeneous primary population. Here we tested the hypothesis that cell-based delivery of a controlled VEGF level could induce normal angiogenesis in the heart, while preventing the development of angiomas. Freshly isolated human adipose tissue-derived stem cells (ASC) were transduced with retroviral vectors expressing either rat VEGF linked to a FACS-quantifiable cell-surface marker (a truncated form of CD8) or CD8 alone as control (CTR). VEGF-expressing cells were FACS-purified to generate populations producing either a specific VEGF level (SPEC) or uncontrolled heterogeneous levels (ALL). Fifteen nude rats underwent intramyocardial injection of 10(7) cells. Histology was performed after 4 weeks. Both the SPEC and ALL cells produced a similar total amount of VEGF, and both cell types induced a 50%-60% increase in both total and perfused vessel density compared to CTR cells, despite very limited stable engraftment. However, homogeneous VEGF expression by SPEC cells induced only normal and stable angiogenesis. Conversely, heterogeneous expression of a similar total amount by the ALL cells caused the growth of numerous angioma-like structures. These results suggest that controlled VEGF delivery by FACS-purified ASC may be a promising strategy to achieve safe therapeutic angiogenesis in the heart.


Subject(s)
Gene Expression , Myocardium/metabolism , Neovascularization, Physiologic/genetics , Vascular Endothelial Growth Factor A/genetics , Adipocytes/cytology , Adipocytes/metabolism , Animals , Cell Survival , Flow Cytometry , Gene Order , Genetic Vectors/genetics , Humans , Inflammation , Male , Myocardium/pathology , Neovascularization, Pathologic , Perfusion , Phenotype , Rats , Stem Cell Transplantation , Stem Cells/cytology , Stem Cells/metabolism , Transduction, Genetic , Transplantation, Heterologous
2.
J Cardiothorac Surg ; 7: 59, 2012 Jun 25.
Article in English | MEDLINE | ID: mdl-22731778

ABSTRACT

BACKGROUND: Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results. METHODS: The sternal ZipFix(TM) System is based on the cable-tie principle. It primarily consists of biocompatible Poly-Ether-Ether-Ketone implants and is predominantly used peristernally through the intercostal space. The system provides a large implant-to-bone contact for better force distribution and for avoiding bone cut through. RESULTS: 50 patients were closed with the ZipFix(TM) system. No sternal instability was observed at 30 days. Two patients developed a mediastinitis that necessitated the removal of the device; however, the ZipFix(TM) were intact and the sternum remained stable. CONCLUSIONS: In our initial evaluation, the short-term results have shown that the sternal ZipFix(TM) can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure.


Subject(s)
Bone Wires , Cardiac Surgical Procedures/instrumentation , Internal Fixators , Sternum/surgery , Wound Closure Techniques/instrumentation , Adult , Aged , Aged, 80 and over , Benzophenones , Cardiac Surgical Procedures/methods , Equipment Design , Female , Humans , Ketones , Male , Materials Testing , Middle Aged , Polyethylene Glycols , Polymers , Sternotomy , Wound Closure Techniques/statistics & numerical data
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