CardioCell is sponsoring several pre-clinical studies to observe how its itMSCs perform for different cardiovascular indications. Results from two studies were accepted for presentation at the European Society of Cardiology (ESC) Congress 2016.
“Mesenchymal stem cells grown under chronic hypoxia improve LV function and inhibit adverse remodeling in mice with chronic ischemic cardiomyopathy”
The hypothesis of this pre-clinical study was designed to determine whether intravenous (IV) itMSC delivery improves myocardial function.
Results using a murine model prove the validity of the hypothesis that IV injection of itMSCs exerts beneficial effects on cardiac function in ischemic cardiomyopathy. The data suggest that excessive inflammation is an important cause of the progressive cardiac dysfunction seen in the control group and that itMSCs exert beneficial cardiac effects — at least, in part — by their systemic anti-inflammatory effects.
Authors: Michael J. Lipinski1, Dror Luger1, Peter C. Westman1, Sergey Sikora2, Ron Waksman1, Stephen E. Epstein1
(1) Washington Hospital Center, Washington, United States of America (2) CardioCell Inc, San Diego, United States of America
“Mesenchymal stem cells grown under chronic hypoxia traffic to regions of myocardial infarction, suppress splenic natural killer cells, and attenuate adverse remodeling in mice with large acute MI”
Stem cells are commonly thought to improve cardiac outcomes by myocardial regeneration or other direct effects from stem cells engrafting themselves in the myocardium. Thus, the concept that the greater the number of myocardial engrafted stem cell the better. Since IV MSC delivery results in very low numbers of cells engrafting in damaged myocardium, catheter- or surgical-based stem cell delivery has been – with rare exception – the sole delivery strategy tested in clinical trials. In a paradigm shift, this study tested the validity of two hypotheses:
Intravenously administered MSCs grown under chronic hypoxic conditions improve myocardial function and adverse remodeling in a murine acute myocardial infarction (AMI) model.
If functional benefit occurs, MSC-induced systemic anti-inflammatory effects play an important mechanistic role.
Both hypotheses were proven to be valid.
Results using a murine model show that IV injection of itMSCs improve cardiac function following an AMI by:
preventing the deterioration in left ventricular function and the progressive adverse remodeling that occurs in mice with large infarcts
modulating the inflammatory response that develops consequent to the acute myocardial injury
reducing the number of natural killer (NK) cells, which are key mediators of inflammation
In separate experiments, antibody-induced reduction in NK cells led to the same beneficial myocardial effects, demonstrating the itMSC-induced decrease in NK cells play a causal role in the observed beneficial myocardial effects produced by MSCs.
Authors: Michael J. Lipinski1, Dror Luger1, Peter C. Westman1, David K. Glover2, Julien Dimastromatteo2, Juan Carlos Frias3, M. Teresa Albelda4, Sergey Sikora5, Ron Waksman1, Stephen E. Epstein1
(1) Washington Hospital Center, Washington, United States of America (2) University of Virginia, Charlottesville, United States of America (3) CEU Universidad Cardenal Herrera, Valencia, Spain (4) University of Valencia, Valencia, Spain (5) CardioCell Inc, San Diego, United States of America
Results were published in Circulation Research. (Circulation Research. 2017;CIRCRESAHA.117.310599) © 2017 by American Heart Association, Inc.