OBJECTIVES: The aim of this study was to investigate whether a fibrinogen biomatrix improves the transplantation effectiveness of induced pluripotent stem cells (iPSCs) in a model of myocardial infarction. BACKGROUND: Early retention, engraftment, and cell proliferation are important factors for successful cardiac stem cell therapy. Common transplantation techniques involve the direction injection of cells in aqueous media. However, this approach yields low retention and variable cell biodistribution, leading to reduced grafts that are unable to sufficiently regenerate damaged myocardium. Biologically compatible scaffolds that improve the retention of injected cells can improve cardiac stem cell therapy. METHODS: Murine iPSCs were transfected for luciferase reporter gene expression. First, in vitro experiments were performed comparing cell viability in fibrinogen and medium. Second, iPSCs were transplanted intramyocardially by direct injection into ischemic myocardium of immunodeficient mice, following permanent left coronary artery ligation. Cells were delivered in medium or fibrinogen. Follow-up included graft assessment by bioluminescence imaging, the evaluation of cardiac function by magnetic resonance imaging, and histology to evaluate graft size and determine the extent of myocardial scarring. RESULTS: In vitro experiments showed proliferation of iPSCs in fibrinogen from 6.4×10(3)±8.0×10(2) after 24 h to 2.1×10(4)±3.2×10(3) after 72 h. Early cardiac cell amount in control group animals was low (23.7%±0.7%) with massive cell accumulation in the right (46.3%±1.0%) and the left lung (30.0%±0.6%). When iPSCs were injected applying the fibrinogen biomatrix, intramyocardial cell amount was increased (66.3%±0.9%) with demonstrable graft proliferation over the experimental time course. Left ventricle-function was higher in the fibrinogen group (42.9%±2.8%), also showing a higher fraction of refilled infarcted-area (66.9%±2.7%). CONCLUSIONS: The fibrinogen biomatrix improved cardiac iPSc retention, sustaining functional improvement and cellular refill of infarcted myocardium. Therefore, fibrinogen can be considered an ideal biological scaffold for intramyocardial stem cell transplantations.
OBJECTIVES: The aim of this study was to investigate whether a fibrinogen biomatrix improves the transplantation effectiveness of induced pluripotent stem cells (iPSCs) in a model of myocardial infarction. BACKGROUND: Early retention, engraftment, and cell proliferation are important factors for successful cardiac stem cell therapy. Common transplantation techniques involve the direction injection of cells in aqueous media. However, this approach yields low retention and variable cell biodistribution, leading to reduced grafts that are unable to sufficiently regenerate damaged myocardium. Biologically compatible scaffolds that improve the retention of injected cells can improve cardiac stem cell therapy. METHODS:Murine iPSCs were transfected for luciferase reporter gene expression. First, in vitro experiments were performed comparing cell viability in fibrinogen and medium. Second, iPSCs were transplanted intramyocardially by direct injection into ischemic myocardium of immunodeficientmice, following permanent left coronary artery ligation. Cells were delivered in medium or fibrinogen. Follow-up included graft assessment by bioluminescence imaging, the evaluation of cardiac function by magnetic resonance imaging, and histology to evaluate graft size and determine the extent of myocardial scarring. RESULTS: In vitro experiments showed proliferation of iPSCs in fibrinogen from 6.4×10(3)±8.0×10(2) after 24 h to 2.1×10(4)±3.2×10(3) after 72 h. Early cardiac cell amount in control group animals was low (23.7%±0.7%) with massive cell accumulation in the right (46.3%±1.0%) and the left lung (30.0%±0.6%). When iPSCs were injected applying the fibrinogen biomatrix, intramyocardial cell amount was increased (66.3%±0.9%) with demonstrable graft proliferation over the experimental time course. Left ventricle-function was higher in the fibrinogen group (42.9%±2.8%), also showing a higher fraction of refilled infarcted-area (66.9%±2.7%). CONCLUSIONS: The fibrinogen biomatrix improved cardiac iPSc retention, sustaining functional improvement and cellular refill of infarcted myocardium. Therefore, fibrinogen can be considered an ideal biological scaffold for intramyocardial stem cell transplantations.
Authors: Wes Hudson; Maria C Collins; Dorian deFreitas; You S Sun; Barbara Muller-Borer; Alan P Kypson Journal: J Surg Res Date: 2007-08-23 Impact factor: 2.192
Authors: Ingo Kutschka; Ian Y Chen; Theo Kofidis; Takayasu Arai; Georges von Degenfeld; Ahmad Y Sheikh; Stephen L Hendry; Jeremy Pearl; Grant Hoyt; Ramachadra Sista; Phillip C Yang; Helen M Blau; Sanjiv S Gambhir; Robert C Robbins Journal: Circulation Date: 2006-07-04 Impact factor: 29.690
Authors: Ingo Kutschka; Theo Kofidis; Ian Y Chen; Georges von Degenfeld; Monika Zwierzchoniewska; Grant Hoyt; Takayasu Arai; Darren R Lebl; Stephen L Hendry; Ahmad Y Sheikh; David T Cooke; Andrew Connolly; Helen M Blau; Sanjiv S Gambhir; Robert C Robbins Journal: Circulation Date: 2006-07-04 Impact factor: 29.690
Authors: Linda W van Laake; Robert Passier; Jantine Monshouwer-Kloots; Marcel G Nederhoff; Dorien Ward-van Oostwaard; Loren J Field; Cees J van Echteld; Pieter A Doevendans; Christine L Mummery Journal: Nat Protoc Date: 2007 Impact factor: 13.491
Authors: Junya Takagawa; Yan Zhang; Maelene L Wong; Richard E Sievers; Neel K Kapasi; Yan Wang; Yerem Yeghiazarians; Randall J Lee; William Grossman; Matthew L Springer Journal: J Appl Physiol (1985) Date: 2007-03-08
Authors: Andreas Martens; Sebastian V Rojas; Hassina Baraki; Christian Rathert; Natalie Schecker; Sara Rojas Hernandez; Kristin Schwanke; Robert Zweigerdt; Ulrich Martin; Shunsuke Saito; Axel Haverich; Ingo Kutschka Journal: PLoS One Date: 2014-08-04 Impact factor: 3.240
Authors: Sebastian V Rojas; George Kensah; Alexander Rotaermel; Hassina Baraki; Ingo Kutschka; Robert Zweigerdt; Ulrich Martin; Axel Haverich; Ina Gruh; Andreas Martens Journal: PLoS One Date: 2017-05-11 Impact factor: 3.240
Authors: Pallavi Pushp; Diogo E S Nogueira; Carlos A V Rodrigues; Frederico C Ferreira; Joaquim M S Cabral; Mukesh Kumar Gupta Journal: Stem Cell Rev Rep Date: 2020-10-23 Impact factor: 5.739