Cajetan Immanuel Lang1,2, Markus Wolfien3, Anne Langenbach4, Paula Müller2, Olaf Wolkenhauer3,5, Arash Yavari6,7,8, Hüseyin Ince1, Gustav Steinhoff2,9, Bernd Joachim Krause10, Robert David2,9, Änne Glass11. 1. Department of Cardiology, University Hospital Rostock, Rostock, Germany. 2. Reference and Translation Center for Cardiac Stem Cell Therapy, University of Rostock, Rostock, Germany. 3. Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany. 4. Department of Anaesthesia and Intensive Care Medicine, University Hospital Rostock, Rostock, Germany. 5. Stellenbosch Institute of Advanced Study, Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa. 6. Experimental Therapeutics, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. 7. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. 8. The Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. 9. Department Life, Light and Matter of the Interdisciplinary Faculty at Rostock University Rostock, Rostock, Germany. 10. Department of Nuclear Medicine, University Hospital Rostock, Rostock, Germany. 11. Institute for Biostatistics and Informatics in Medicine and Ageing Research, University Hospital Rostock, Rostock, Germany.
Abstract
AIMS: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field. METHODS AND RESULTS: A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7-13.8) compared with control animals. CONCLUSION: The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.
AIMS: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field. METHODS AND RESULTS: A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7-13.8) compared with control animals. CONCLUSION: The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.
Authors: Rajshekhar A Kore; Jeffrey C Henson; Rabab N Hamzah; Robert J Griffin; Alan J Tackett; Zufeng Ding; Jawahar L Mehta Journal: Sci Rep Date: 2019-12-17 Impact factor: 4.996
Authors: Maximilian Fischer; Tobias Weinberger; Guido Boening; Andrei Todica; Denise Messerer; Mathias J Zacherl; Christian Schulz; Steffen Massberg; Peter Bartenstein; Sebastian Lehner Journal: Ann Nucl Med Date: 2022-03-30 Impact factor: 2.258