Cardiomyogenesis in the adult human heart.
BACKGROUND
The ability of the human heart to regenerate large quantities of myocytes remains controversial, and the extent of myocyte renewal claimed by different laboratories varies from none to nearly 20% per year.


OBJECTIVE
To address this issue, we examined the percentage of myocytes, endothelial cells, and fibroblasts labeled by iododeoxyuridine in postmortem samples obtained from cancer patients who received the thymidine analog for therapeutic purposes. Additionally, the potential contribution of DNA repair, polyploidy, and cell fusion to the measurement of myocyte regeneration was determined.


RESULTS
The fraction of myocytes labeled by iododeoxyuridine ranged from 2.5% to 46%, and similar values were found in fibroblasts and endothelial cells. An average 22%, 20%, and 13% new myocytes, fibroblasts, and endothelial cells were generated per year, suggesting that the lifespan of these cells was approximately 4.5, 5, and 8 years, respectively. The newly formed cardiac cells showed a fully differentiated adult phenotype and did not express the senescence-associated protein p16(INK4a). Moreover, measurements by confocal microscopy and flow cytometry documented that the human heart is composed predominantly of myocytes with 2n diploid DNA content and that tetraploid and octaploid nuclei constitute only a small fraction of the parenchymal cell pool. Importantly, DNA repair, ploidy formation, and cell fusion were not implicated in the assessment of myocyte regeneration.


CONCLUSIONS
Our findings indicate that the human heart has a significant growth reserve and replaces its myocyte and nonmyocyte compartment several times during the course of life.
Department of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA. jkajstura@partners.org
Jan
J
Kajstura
Konrad
K
Urbanek
Shira
S
Perl
Toru
T
Hosoda
Hanqiao
H
Zheng
Barbara
B
Ogórek
João
J
Ferreira-Martins
Polina
P
Goichberg
Carlos
C
Rondon-Clavo
Fumihiro
F
Sanada
Domenico
D
D'Amario
Marcello
M
Rota
Federica
F
Del Monte
Donald
D
Orlic
John
J
Tisdale
Annarosa
A
Leri
Piero
P
Anversa
D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D001344:Autopsy; D016923:Cell Death; D002459:Cell Fusion; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D024510:Muscle Development / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010641:Phenotype; D011123:Polyploidy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D013997:Time Factors; D055815:Young Adult
D011838:Radiation-Sensitizing Agents; D007065:Idoxuridine