About Us
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Belfer Gene Therapy Core Facility (BGTCF) is a cutting-edge genetic medicine research facility.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Belfer Gene Therapy Core Facility (BGTCF) is a cutting-edge genetic medicine research facility.
Publication Type | Academic Article |
Authors | Mathison M, Gersch R, Nasser A, Lilo S, Korman M, Fourman M, Hackett N, Shroyer K, Yang J, Ma Y, Crystal R, Rosengart T |
Journal | J Am Heart Assoc |
Volume | 1 |
Issue | 6 |
Pagination | e005652 |
Date Published | 12/19/2012 |
ISSN | 2047-9980 |
Keywords | Myocardial Infarction, Neovascularization, Physiologic, Transcription Factors, Vascular Endothelial Growth Factor A, Ventricular Function |
Abstract | BACKGROUND: In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. METHODS AND RESULTS: Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). CONCLUSIONS: VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone. |
DOI | 10.1161/JAHA.112.005652 |
PubMed ID | 23316332 |
PubMed Central ID | PMC3540681 |