CSB Seminar: Dr. David Courtman, Ottawa Research Institute, Ottawa

“Cell and Cell Based Gene Therapies for Cardio-Pulmonary Disease:
Regulation of Cell Phenotype by Extracellular Matrix“

Host:  Prof. Maurice Ringuette <maurice.ringuette@utoronto.ca>

Abstract:
The loss of peripheral vasculature is the hallmark of serious cardiovascular diseases and can lead to peripheral and myocardial ischemia or if occurring in the lung pulmonary hypertension (PH), an often progressive and fatal disease culminating in right heart failure. Autologous cells derived from the circulation and modified in culture to take on an endothelial phenotype hold promise for the regeneration of lost vasculature. The therapeutic application of these putative endothelial progenitor cells (EPCs) may provide some benefit, yet preclinical studies suggest that patient derived autologous cells are less effective stimulators of vascular repair. We have therefore pioneered the development of gene enhanced autologous cell based treatments for pulmonary hypertension and myocardial ischemia. Our first-in-human clinical trials are on going, with early results demonstrating safety and efficacy in PH patients.  A major limitation of these cell therapies is the extremely low rate of cell engraftment and survival in the target organ. We have hypothesized that modifying the cell surface by either growth on selected matrices or by encapsulation in an engineered provisional matrix will enhance cell survival, differentiation, and targeted organ engraftment ultimately leading to improved tissue regeneration. We found that eNOS expression in these EPCs is regulated by extracellular matrix. Thus the combination of autologous EPCs, gene therapy, and matricellular protein conditioning could be a promising method of  developing a cell therapy with increased potency for vascular regeneration.

Video Conferencing at UTM (DV3138) & UTSc (MW229)