A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease
Abstract
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. 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 14 C 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.
Article Details
Authors (26)
Wouter Derks
Centers for Regenerative Therapies Dresden (W.D., F.R., P.H., A.H., L.P., I.S., O.B.), Technische Universität Dresden, Germany.
Julian Rode
Information Services and High-Performance Computing (J.R., F.R., L.B.), Technische Universität Dresden, Germany.
Sofia Collin
Departments of Cell and Molecular Biology (S.C., E.L., E.G., J.F., O.B.), Stockholm, Sweden.
Fabian Rost
Paula Heinke
Centers for Regenerative Therapies Dresden (W.D., F.R., P.H., A.H., L.P., I.S., O.B.), Technische Universität Dresden, Germany.
Anjana Hariharan
Centers for Regenerative Therapies Dresden (W.D., F.R., P.H., A.H., L.P., I.S., O.B.), Technische Universität Dresden, Germany.
Lauren Pickel
Irina Simonova
Centers for Regenerative Therapies Dresden (W.D., F.R., P.H., A.H., L.P., I.S., O.B.), Technische Universität Dresden, Germany.
Enikő Lázár
Evan Graham
Departments of Cell and Molecular Biology (S.C., E.L., E.G., J.F., O.B.), Stockholm, Sweden.
Ramadan Jashari
European Homograft Bank, Brussels, Belgium (R.J.).
Michaela Andrä
Department of Cardiothoracic and Vascular Surgery, Klinikum Klagenfurt and Section for Surgical Research Medical University Graz, Austria (M.A.).
Anders Jeppsson
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
Mehran Salehpour
Department of Physics and Astronomy, Applied Nuclear Physics, Uppsala University, Uppsala, Sweden (M.S.).
Kanar Alkass
Oncology-Pathology (K.A., H.D.), Karolinska Institute, Stockholm, Sweden.
Henrik Druid
Oncology-Pathology (K.A., H.D.), Karolinska Institute, Stockholm, Sweden.
Christos P. Kyriakopoulos
Divisions of Cardiovascular Medicine and Cardiothoracic Surgery, University of Utah Health and School of Medicine (C.P.K., I.T., C.H.S., S.D.), Salt Lake City.
Iosif Taleb
University of Utah School of Medicine, Salt Lake City, Utah, United States
Thirupura S. Shankar
Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah, Salt Lake City, UT, USA.
Craig H. Selzman
Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah, Salt Lake City, UT, USA.
Hesham Sadek
The Sarver Heart Center and The Department of Internal Medicine/Cardiology, The University of Arizona College of Medicine Tucson, Arizona (H.S.).
Stefan Jovinge
Scania University Sweden, Lund, Sweden
Lutz Brusch
Information Services and High-Performance Computing (J.R., F.R., L.B.), Technische Universität Dresden, Germany.
Jonas Frisén
Departments of Cell and Molecular Biology (S.C., E.L., E.G., J.F., O.B.), Stockholm, Sweden.
Stavros Drakos
U OF U SCHOOL OF MEDICINE, Salt Lake Cty, Utah, United States
Olaf Bergmann
Centers for Regenerative Therapies Dresden (W.D., F.R., P.H., A.H., L.P., I.S., O.B.), Technische Universität Dresden, Germany.