2009 April 3 | Olaf Bergmann, Ratan D. Bhardwaj, Samuel Bernard, Sofia Zdunek, Fanie Barnabé-Heider, Stuart Walsh, Joel Zupicich, Kanar Alkass, Bruce A. Buchholz, Henrik Druid, Stefan Jovinge, Jonas Frisén
A study published in Science (2009) provides evidence that cardiomyocytes in humans undergo renewal throughout life. By analyzing the integration of carbon-14 (¹⁴C), produced by nuclear bomb tests during the Cold War, into DNA, researchers determined the age of cardiomyocytes in humans. The results show that cardiomyocytes renew gradually, with a turnover rate of 1% annually at age 20 decreasing to 0.3% at age 75. Less than 50% of cardiomyocytes are replaced during a normal lifespan. This suggests that the adult human heart has the capacity to generate new cardiomyocytes, which could be harnessed for therapeutic strategies in cardiac pathologies.
Myocardial damage often leads to chronic heart failure due to loss and insufficient regeneration of cardiomyocytes. Efforts to develop cardiomyocyte replacement therapies include cell transplantation and promoting endogenous regenerative processes. While cell transplantation strategies are advancing, stimulating endogenous regeneration is attractive as it could provide a non-invasive therapy. However, it is unclear whether such strategies are realistic, as it has been difficult to establish whether cardiomyocytes can be generated after the perinatal period in humans.
Stem/progenitor cells in the adult human myocardium have the potential to generate cardiomyocytes in vitro. Additionally, mature cardiomyocytes have been suggested to reenter the cell cycle and duplicate. However, studies in rodents have yielded conflicting results regarding postnatal cardiomyocyte generation. A recent genetic labeling study showed cardiomyocyte renewal after myocardial injury but not during one year in the healthy mouse.
The study used ¹⁴C from nuclear bomb tests in genomic DNA of human myocardial cells to determine cell birth dates. ¹⁴C levels in the atmosphere increased dramatically during the Cold War, and have since decreased. The ¹⁴C concentration in the human body mirrors atmospheric levels, allowing for retrospective dating of cells. DNA synthesis was detected in human heart cells, indicating postnatal cell turnover.
Cardiomyocytes make up about 20% of all cells in the human myocardium, so data on DNA synthesis cannot directly infer cardiomyocyte renewal. Researchers specifically dated cardiomyocytes using flow cytometry and antibodies against cardiomyocyte-specific proteins. The results showed that cardiomyocytes are renewed throughout life, with a gradual decrease in turnover rate with age.
The study also found that cardiomyocyte DNA synthesis detected by ¹⁴C analysis cannot be explained by an increase in cardiomyocyte number or binucleation. Instead, it is likely due to renewal. The data indicate that cardiomyocytes are renewed at a rate of approximately 1% per year at age 20 and 0.3% at age 75. This suggests that the majority of cardiomyocytes will never be exchanged during a normal lifespan. The study also found that non-cardiomyocytes have a muchA study published in Science (2009) provides evidence that cardiomyocytes in humans undergo renewal throughout life. By analyzing the integration of carbon-14 (¹⁴C), produced by nuclear bomb tests during the Cold War, into DNA, researchers determined the age of cardiomyocytes in humans. The results show that cardiomyocytes renew gradually, with a turnover rate of 1% annually at age 20 decreasing to 0.3% at age 75. Less than 50% of cardiomyocytes are replaced during a normal lifespan. This suggests that the adult human heart has the capacity to generate new cardiomyocytes, which could be harnessed for therapeutic strategies in cardiac pathologies.
Myocardial damage often leads to chronic heart failure due to loss and insufficient regeneration of cardiomyocytes. Efforts to develop cardiomyocyte replacement therapies include cell transplantation and promoting endogenous regenerative processes. While cell transplantation strategies are advancing, stimulating endogenous regeneration is attractive as it could provide a non-invasive therapy. However, it is unclear whether such strategies are realistic, as it has been difficult to establish whether cardiomyocytes can be generated after the perinatal period in humans.
Stem/progenitor cells in the adult human myocardium have the potential to generate cardiomyocytes in vitro. Additionally, mature cardiomyocytes have been suggested to reenter the cell cycle and duplicate. However, studies in rodents have yielded conflicting results regarding postnatal cardiomyocyte generation. A recent genetic labeling study showed cardiomyocyte renewal after myocardial injury but not during one year in the healthy mouse.
The study used ¹⁴C from nuclear bomb tests in genomic DNA of human myocardial cells to determine cell birth dates. ¹⁴C levels in the atmosphere increased dramatically during the Cold War, and have since decreased. The ¹⁴C concentration in the human body mirrors atmospheric levels, allowing for retrospective dating of cells. DNA synthesis was detected in human heart cells, indicating postnatal cell turnover.
Cardiomyocytes make up about 20% of all cells in the human myocardium, so data on DNA synthesis cannot directly infer cardiomyocyte renewal. Researchers specifically dated cardiomyocytes using flow cytometry and antibodies against cardiomyocyte-specific proteins. The results showed that cardiomyocytes are renewed throughout life, with a gradual decrease in turnover rate with age.
The study also found that cardiomyocyte DNA synthesis detected by ¹⁴C analysis cannot be explained by an increase in cardiomyocyte number or binucleation. Instead, it is likely due to renewal. The data indicate that cardiomyocytes are renewed at a rate of approximately 1% per year at age 20 and 0.3% at age 75. This suggests that the majority of cardiomyocytes will never be exchanged during a normal lifespan. The study also found that non-cardiomyocytes have a much