Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF <sub>164</sub>
-
- Veronica Sacchi
- Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;
-
- Rainer Mittermayr
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;
-
- Joachim Hartinger
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;
-
- Mikaël M. Martino
- Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
-
- Kristen M. Lorentz
- Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
-
- Susanne Wolbank
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;
-
- Anna Hofmann
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;
-
- Remo A. Largo
- Departments of dUrology and
-
- Jeffrey S. Marschall
- Obstetrics, Zurich University Hospital, CH-8091 Zurich, Switzerland; and
-
- Elena Groppa
- Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;
-
- Roberto Gianni-Barrera
- Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;
-
- Martin Ehrbar
- Obstetrics, Zurich University Hospital, CH-8091 Zurich, Switzerland; and
-
- Jeffrey A. Hubbell
- Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
-
- Heinz Redl
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;
-
- Andrea Banfi
- Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;
説明
<jats:title>Significance</jats:title> <jats:p>Inducing the growth of new blood vessels by specific factors is an attractive strategy to restore blood flow in ischemic tissues. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, yet clinical trials of VEGF gene delivery failed. Major challenges include the need to control the tissue distribution of factor dose and the duration of expression. Here, we developed a highly tunable fibrin-based platform to precisely control the dose and duration of VEGF protein delivery in tissues. Optimized delivery of fibrin-bound VEGF ensured normal, stable, and functional angiogenesis and improved perfusion of ischemic tissues, without genetic modification and with limited duration of VEGF delivery. These findings suggest a strategy to improve both safety and efficacy of therapeutic angiogenesis.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 111 (19), 6952-6957, 2014-04-28
Proceedings of the National Academy of Sciences
