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Updated: May 13, 2026
Simultaneous Assessment of Cardiomyocyte DNA Synthesis and Ploidy: A Method to Assist Quantification of Cardiomyocyte Regeneration and Turnover
Published on: May 23, 2016
Mammalian heart renewal by pre-existing cardiomyocytes
Samuel E Senyo1, Matthew L Steinhauser, Christie L Pizzimenti
1Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
Insights
New heart cells (cardiomyocytes) arise from existing ones, not stem cells, through division. This cardiomyocyte replacement occurs slowly during aging and increases near injury sites.
Area of Science:
- Cardiovascular Biology
- Cellular Biology
- Regenerative Medicine
Background:
- Recent studies indicate adult mammals generate new heart cells (cardiomyocytes), but the rate and source remain debated.
- Hypotheses include high stem cell activity versus low-rate division of existing cardiomyocytes.
Purpose of the Study:
- To determine the frequency and source of new cardiomyocyte generation in adult mammals.
- To investigate cardiomyocyte genesis during normal aging and in response to myocardial injury.
Main Methods:
- Combined genetic fate-mapping with stable isotope labeling (pulse-chase approach).
- Utilized multi-isotope imaging mass spectrometry to track cell division and origin.
- Analyzed cardiomyocyte proliferation, ploidy, and multinucleation.
Main Results:
- Cardiomyocyte genesis occurs at a low rate through the division of pre-existing cardiomyocytes during normal aging.
- This division process increases adjacent to areas of myocardial injury.
- Cell cycle activity resulted in polyploidy, multinucleation, and the formation of new diploid, mononucleate cardiomyocytes.
Conclusions:
- Pre-existing cardiomyocytes are the primary source of cardiomyocyte replacement in normal mammalian heart homeostasis.
- Existing cardiomyocytes also serve as the dominant source for cardiomyocyte replacement following myocardial injury.
- This finding clarifies the endogenous mechanism of cardiomyocyte turnover and repair.
Abstract:
Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
