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Updated: May 27, 2026

Pipeline for Multi-Scale Three-Dimensional Anatomic Study of the Human Heart
Published on: June 28, 2024
Prometheus's heart: what lies beneath
Lucio Barile1, Vincenzo Lionetti
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Insights
Adult cardiomyocytes can renew through slow turnover, challenging the long-held belief that heart cells do not regenerate. This cardiac regeneration involves progenitor cells, but human recovery remains limited.
Area of Science:
- Cardiology
- Cell Biology
- Regenerative Medicine
Background:
- Heart attacks cause cell death and scar tissue, impairing heart function.
- Historically, adult cardiomyocytes were believed incapable of regeneration after birth.
- Previous studies aimed to disprove cardiomyocyte renewal in humans.
Purpose of the Study:
- To investigate the potential for cardiomyocyte renewal in adult hearts.
- To explore the mechanisms underlying myocardial regeneration.
- To assess the regenerative capacity following heart injury.
Main Methods:
- Initial observations using light microscopy.
- Confirmation with advanced imaging and cellular technologies.
- Analysis of cardiomyocyte turnover and progenitor cell activity.
Main Results:
- Evidence of cardiomyocyte mitosis (cell division) near injury sites.
- Discovery of a slow cardiomyocyte turnover even without damage.
- Identification of cardiac progenitor cells driving this renewal process.
Conclusions:
- Adult cardiomyocytes do undergo slow renewal, contradicting the dogma of a terminally differentiated heart.
- Cardiac progenitor cells play a crucial role in cardiomyocyte turnover.
- Limited functional recovery post-injury highlights weak human regenerative potential, necessitating new therapeutic strategies.
Abstract:
A heart attack kills off many cells in the heart. Parts of the heart become thin and fail to contract properly following the replacement of lost cells by scar tissue. However, the notion that the same adult cardiomyocytes beat throughout the lifespan of the organ and organism, without the need for a minimum turnover, gives way to a fascinating investigations. Since the late 1800s, scientists and cardiologists wanted to demonstrate that the cardiomyocytes cannot be generated after the perinatal period in human beings. This curiosity has been passed down in subsequent years and has motivated more and more accurate studies in an attempt to exclude the presence of renewed cardiomyocytes in the tissue bordering the ischaemic area, and then to confirm the dogma of the heart as terminally differentiated organ. Conversely, peri-lesional mitosis of cardiomyocytes were discovered initially by light microscopy and subsequently confirmed by more sophisticated technologies. Controversial evidence of mechanisms underlying myocardial regeneration has shown that adult cardiomyocytes are renewed through a slow turnover, even in the absence of damage. This turnover is ensured by the activation of rare clusters of progenitor cells interspersed among the cardiac cells functionally mature. Cardiac progenitor cells continuously interact with each other, with the cells circulating in the vessels of the coronary microcirculation and myocardial cells in auto-/paracrine manner. Much remains to be understood; however, the limited functional recovery in human beings after myocardial injury clearly demonstrates weak regenerative potential of cardiomyocytes and encourages the development of new approaches to stimulate this process.
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