title: Mesenchymal stem cell delivery strategies to promote cardiac regeneration following ischemic injury.
abstract: Myocardial infarction (MI) is one of the leading causes of mortality worldwide and is associated with irreversible cardiomyocyte death and pathological remodeling of cardiac tissue. In the past 15 years, several animal models have been developed for pre-clinical testing to assess the potential of stem cells for functional tissue regeneration and the attenuation of left ventricular remodeling. The promising results obtained in terms of improved cardiac function, neo-angiogenesis and reduction in infarct size have motivated the initiation of clinical trials in humans. Despite the potential, the results of these studies have highlighted that the effective delivery and retention of viable cells within the heart remain significant challenges that have limited the therapeutic efficacy of cell-based therapies for treating the ischemic myocardium. In this review, we discuss key elements for designing clinically translatable cell-delivery approaches to promote myocardial regeneration. Key topics addressed include cell selection, with a focus on mesenchymal stem cells derived from the bone marrow (bMSCs) and adipose tissue (ASCs), including a discussion of their potential mechanisms of action. Natural and synthetic biomaterials that have been investigated as injectable cell delivery vehicles for cardiac applications are critically reviewed, including an analysis of the role of the biomaterials themselves in the therapeutic scheme.
authors.affiliation: Department of Chemical Engineering, Queen's University, 19 Division Street, Kingston, Ontario, Canada K7L 3N6; Human Mobility Research Centre, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7.
authors.forename: Valerio
authors.initials: V
authors.lastname: Russo
authors.affiliation: Department of Chemical Engineering, Queen's University, 19 Division Street, Kingston, Ontario, Canada K7L 3N6; Human Mobility Research Centre, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7.
authors.forename: Stuart
authors.initials: S
authors.lastname: Young
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: Department of Chemical Engineering, Queen's University, 19 Division Street, Kingston, Ontario, Canada K7L 3N6; Human Mobility Research Centre, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Amsden
authors.affiliation: Department of Chemical Engineering, Queen's University, 19 Division Street, Kingston, Ontario, Canada K7L 3N6; Department of Chemical and Biochemical Engineering, Thompson Engineering Building, The University of Western Ontario, London, Ontario, Canada N6A 5B9; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1. Electronic address: lauren.flynn@uwo.ca.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Flynn
mesh_terms: D000818:Animals; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*
keywords: Angiogenesis; Cardiac tissue engineering; Cell encapsulation; Injectable biomaterials; Mesenchymal stem cell