A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease

人类心脏病中潜在的心肌细胞再生潜能

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作者:Wouter Derks #, Julian Rode #, Sofia Collin #, Fabian Rost, Paula Heinke, Anjana Hariharan, Lauren Pickel, Irina Simonova, Enikő Lázár, Evan Graham, Ramadan Jashari, Michaela Andrä, Anders Jeppsson, Mehran Salehpour, Kanar Alkass, Henrik Druid, Christos P Kyriakopoulos, Iosif Taleb, Thirupura S Shan

Background

Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

Conclusions

Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

Methods

We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test-derived 14C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.

Results

We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart. Conclusions: Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

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