title: Gaining myocytes or losing fibroblasts: Challenges in cardiac fibroblast reprogramming for infarct repair.
abstract: Unlike most somatic tissues, the heart possesses a very limited inherent ability to repair itself following damage. Attempts to therapeutically salvage the myocardium after infarction, either by sparing surviving myocytes or by injection of exogenous cells of varied provenance, have met with limited success. Cardiac fibroblasts are numerous, resistant to hypoxia, and amenable to phenotype reprogramming to cardiomyocytes - a potential panacea to an intractable problem. However, the long-term effects of mass conversion of fibroblasts are as-yet unknown. Since fibroblasts play key roles in normal cardiac function, treating these cells as a ready source of replacements for myocytes may have the effect of swapping one problem for another. This review briefly examines the roles of cardiac fibroblasts, recaps the strides made so far in their reprogramming to cardiomyocytes both in vitro and in vivo, and discusses the potential ramifications of large-scale cellular identity swapping. While such therapy offers great promise, the potential repercussions require consideration and careful study.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre and Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H2A6.
authors.forename: Raghu S
authors.initials: RS
authors.lastname: Nagalingam
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre and Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H2A6.
authors.forename: Hamza A
authors.initials: HA
authors.lastname: Safi
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre and Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada R2H2A6. Electronic address: mczubryt@sbrc.ca.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czubryt
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D014945:Wound Healing
keywords: Cardiac fibroblasts; Extracellular matrix; Myocardial infarction; Reprogramming; Transdifferentiation