Measuring cardiomyocyte cell-cycle activity and proliferation in the age of heart regeneration. Am J Physiol Heart Circ Physiol 2022 Apr 01;322(4):H579-H596
Date
02/19/2022Pubmed ID
35179974Pubmed Central ID
PMC8934681DOI
10.1152/ajpheart.00666.2021Scopus ID
2-s2.0-85127729067 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
During the past two decades, the field of mammalian myocardial regeneration has grown dramatically, and with this expanded interest comes increasing claims of experimental manipulations that mediate bona fide proliferation of cardiomyocytes. Too often, however, insufficient evidence or improper controls are provided to support claims that cardiomyocytes have definitively proliferated, a process that should be strictly defined as the generation of two de novo functional cardiomyocytes from one original cardiomyocyte. Throughout the literature, one finds inconsistent levels of experimental rigor applied, and frequently the specific data supplied as evidence of cardiomyocyte proliferation simply indicate cell-cycle activation or DNA synthesis, which do not necessarily lead to the generation of new cardiomyocytes. In this review, we highlight potential problems and limitations faced when characterizing cardiomyocyte proliferation in the mammalian heart, and summarize tools and experimental standards, which should be used to support claims of proliferation-based remuscularization. In the end, definitive establishment of de novo cardiomyogenesis can be difficult to prove; therefore, rigorous experimental strategies should be used for such claims.
Author List
Auchampach J, Han L, Huang GN, Kühn B, Lough JW, O'Meara CC, Payumo AY, Rosenthal NA, Sucov HM, Yutzey KE, Patterson MAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinLu Han PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Caitlin C. O'Meara PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Michaela Patterson PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCell Cycle
Cell Proliferation
Heart
Mammals
Myocytes, Cardiac
Regeneration
