OBJECTIVES: A novel method to magnetically localize endothelial cells at the site of a stented vessel wall was developed. The application of this strategy in a large animal model is described. BACKGROUND: Local delivery of blood-derived endothelial cells has been shown to facilitate vascular healing in animal models. Therapeutic utilization has been limited by an inability to retain cells in the presence of blood flow. We hypothesized that a magnetized stent would facilitate local retention of superparamagnetically labeled cells. METHODS: Cultured porcine endothelial cells were labeled with endocytosed superparamagnetic iron oxide microspheres. A 500:1 microsphere-to-cell ratio was selected for in vivo experiments based on bromo-deoxyuridine incorporation and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assays. Stents were magnetized and implanted in porcine coronary and femoral arteries using standard interventional equipment. Labeled endothelial cells were delivered locally during transient occlusion of blood flow. RESULTS: The delivered cells were found attached to the stent struts and were also distributed within the adjacent denuded vessel wall at 24 h. CONCLUSIONS: Magnetic forces can be used to rapidly place endothelial cells at the site of a magnetized intravascular stent. The delivered cells are retained in the presence of blood flow and also spread to the adjacent injured vessel wall. Potential applications include delivering a cell-based therapeutic effect to the local vessel wall as well as downstream tissue.
OBJECTIVES: A novel method to magnetically localize endothelial cells at the site of a stented vessel wall was developed. The application of this strategy in a large animal model is described. BACKGROUND: Local delivery of blood-derived endothelial cells has been shown to facilitate vascular healing in animal models. Therapeutic utilization has been limited by an inability to retain cells in the presence of blood flow. We hypothesized that a magnetized stent would facilitate local retention of superparamagnetically labeled cells. METHODS: Cultured porcine endothelial cells were labeled with endocytosed superparamagnetic iron oxide microspheres. A 500:1 microsphere-to-cell ratio was selected for in vivo experiments based on bromo-deoxyuridine incorporation and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assays. Stents were magnetized and implanted in porcine coronary and femoral arteries using standard interventional equipment. Labeled endothelial cells were delivered locally during transient occlusion of blood flow. RESULTS: The delivered cells were found attached to the stent struts and were also distributed within the adjacent denuded vessel wall at 24 h. CONCLUSIONS: Magnetic forces can be used to rapidly place endothelial cells at the site of a magnetized intravascular stent. The delivered cells are retained in the presence of blood flow and also spread to the adjacent injured vessel wall. Potential applications include delivering a cell-based therapeutic effect to the local vessel wall as well as downstream tissue.
Authors: Hanna Mannell; Joachim Pircher; Thomas Räthel; Katharina Schilberg; Katrin Zimmermann; Alexander Pfeifer; Olga Mykhaylyk; Bernhard Gleich; Ulrich Pohl; Florian Krötz Journal: Pharm Res Date: 2012-01-25 Impact factor: 4.200
Authors: Carsten Kilgus; Alexandra Heidsieck; Annika Ottersbach; Wilhelm Roell; Christina Trueck; Bernd K Fleischmann; Bernhard Gleich; Philipp Sasse Journal: Pharm Res Date: 2011-12-30 Impact factor: 4.200
Authors: Michael Chorny; Ivan S Alferiev; Ilia Fishbein; Jillian E Tengood; Zoë Folchman-Wagner; Scott P Forbes; Robert J Levy Journal: Pharm Res Date: 2012-01-25 Impact factor: 4.200
Authors: Boris Polyak; Ilia Fishbein; Michael Chorny; Ivan Alferiev; Darryl Williams; Ben Yellen; Gary Friedman; Robert J Levy Journal: Proc Natl Acad Sci U S A Date: 2008-01-08 Impact factor: 11.205
Authors: Michael Chorny; Ilia Fishbein; Richard F Adamo; Scott P Forbes; Zoë Folchman-Wagner; Ivan S Alferiev Journal: Methodist Debakey Cardiovasc J Date: 2012-01
Authors: Catalin Toma; Andrew Fisher; Jianjun Wang; Xucai Chen; Michelle Grata; Jonathan Leeman; Brion Winston; Mehmet Kaya; Huili Fu; Linda Lavery; David Fischer; William R Wagner; Flordeliza S Villanueva Journal: Tissue Eng Part A Date: 2011-02-27 Impact factor: 3.845