Genetic enhancement of stem cell engraftment, survival, and efficacy.
Cell-based therapies for the prevention and treatment of cardiac dysfunction offer the potential to significantly modulate cardiac function and improve outcomes in patients with cardiovascular disease. To date several clinical studies have suggested the potential efficacy of several different stem cell types; however, the benefits seen in clinical trials have been inconsistent and modest. In parallel, preclinical studies have identified key events in the process of cell-based myocardial repair, including stem cell homing, engraftment, survival, paracrine factor release, and differentiation that need to be optimized to maximize cardiac repair and function. The inconsistent and modest benefits seen in clinical trials combined with the preclinical identification of mediators responsible for key events in cell-based cardiac repair offers the potential for cell-based therapy to advance to cell-based gene therapy in an attempt to optimize these key events in the hope of maximizing clinical benefit. Below we discuss potential key events in cardiac repair and the mediators of these events that could be of potential interest for genetic enhancement of stem cell-based cardiac repair.
Penn
Marc S
MS
Skirball Laboratory for Cardiovascular Cellular Therapeutics, Center for Cardiovascular Cellular Therapeutics, NE3, 9500 Euclid Avenue, Cleveland, OH 44195, USA. pennm@ccf.org
Mangi
Abeel A
AA
D002450:Cell Communication; D002465:Cell Movement; D002470:Cell Survival; D018925:Chemokines / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D042783:Endothelial Cells / Q000637:transplantation; D004730:Endothelium, Vascular / Q000293:injuries; D005109:Extracellular Matrix / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000502:physiology; D006082:Graft Enhancement, Immunologic; D006321:Heart / Q000502:physiology; D006331:Heart Diseases / Q000601:surgery*; D006801:Humans; D016023:Integrins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D032383:Myocytes, Cardiac / Q000502:physiology; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012038:Regeneration; D033581:Stem Cell Transplantation
D018925:Chemokines; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins