title: The current state of stem cell therapeutics: Canadian approaches in the international context.
abstract: After ischemic injury, the endogenous repair mechanisms of the human heart are insufficient for meaningful tissue regeneration, so muscle lost is replaced by noncontractile scar tissue. Current treatments for ischemic cardiomyopathy improve quality of life and increase life expectancy, but cannot cure the underlying disease of cardiomyocyte loss. Cellular transplantation is emerging as a valuable therapeutic approach to heal the ischemic heart. Adult bone marrow stem cells are capable of differentiation, regeneration of infarcted myocardium, and induction of myogenesis and angiogenesis, ultimately leading to improved contractility. Positive results from animal studies have prompted several clinical trials to ascertain the safety and feasibility of cell therapy. However, despite all the excitement in stem cell research resulting from initial experimental data and preliminary clinical trials, the mixed results observed have raised many unanswered questions. A major obstacle to the identification of the optimal cell therapy is that the fate of the implanted cells and the nature of their beneficial effects are ill-defined. A better understanding is fundamental for the development of new therapeutic agents, and to optimize stem cell applications. Well-designed and powered double-blinded randomized studies are clearly needed to confirm promising findings from early studies. With several ongoing randomized trials directed toward evaluation of stem cell therapies in patients with acute or chronic ischemic cardiomyopathy, the Canadian initiative represents a milestone.
authors.affiliation: Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada. Electronic address: noiseuxn@videotron.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noiseux
authors.affiliation: Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marquis-Gravel
authors.affiliation: Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Samer
authors.initials: S
authors.lastname: Mansour
authors.affiliation: Department of Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Uswa
authors.initials: U
authors.lastname: Shahzad
authors.affiliation: Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.affiliation: Department of Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Yau
mesh_terms: D000818:Animals; D002170:Canada; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology*; D033581:Stem Cell Transplantation / Q000379:methods*